{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:39:55Z","timestamp":1790372395811,"version":"4.1.0"},"reference-count":221,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2010,8,10]],"date-time":"2010-08-10T00:00:00Z","timestamp":1281398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>An estimated 4 billion episodes of diarrhea occur each year. As a result, 2\u20133 million children and 0.5\u20131 million adults succumb to the consequences of this major healthcare concern. The majority of these deaths can be attributed to toxin mediated diarrhea by infectious agents, such as E. coli, V. cholerae or Rotavirus. Our understanding of the pathophysiological processes underlying these infectious diseases has notably improved over the last years. This review will focus on the cellular mechanism of action of the most common enterotoxins and the latest specific therapeutic approaches that have been developed to contain their lethal effects.<\/jats:p>","DOI":"10.3390\/toxins2082132","type":"journal-article","created":{"date-parts":[[2010,8,10]],"date-time":"2010-08-10T11:31:12Z","timestamp":1281439872000},"page":"2132-2157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Toxin Mediated Diarrhea in the 21st Century: The Pathophysiology of Intestinal Ion Transport in the Course of ETEC, V. cholerae and Rotavirus Infection"],"prefix":"10.3390","volume":"2","author":[{"given":"Sascha","family":"Kopic","sequence":"first","affiliation":[{"name":"Departments of Surgery & Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Geibel","sequence":"additional","affiliation":[{"name":"Departments of Surgery & Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2010,8,10]]},"reference":[{"key":"ref_1","first-page":"197","article-title":"The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000","volume":"81","author":"Kosek","year":"2003","journal-title":"Bull. World Health Organ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1146\/annurev.physiol.62.1.535","article-title":"Chloride secretion by the intestinal epithelium: Molecular basis and regulatory aspects","volume":"62","author":"Barrett","year":"2000","journal-title":"Annu. Rev. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1172\/JCI118294","article-title":"Fluid absorption in isolated perfused colonic crypts","volume":"96","author":"Singh","year":"1995","journal-title":"J. Clin. Invest."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1172\/JCI116966","article-title":"Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastrointestinal tract by in situ hybridization","volume":"93","author":"Strong","year":"1994","journal-title":"J. Clin. Invest."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1152\/physrev.00026.2001","article-title":"Electrolyte transport in the mammalian colon: Mechanisms and implications for disease","volume":"82","author":"Kunzelmann","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"C1294","DOI":"10.1152\/ajpcell.1993.264.5.C1294","article-title":"Origin of cAMP-dependent Cl\u2212 secretion from both crypts and surface epithelia of rat intestine","volume":"264","author":"Kockerling","year":"1993","journal-title":"Am. J. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1146\/annurev.physiol.67.031103.153004","article-title":"Molecular physiology of intestinal Na+\/H+ exchange","volume":"67","author":"Zachos","year":"2005","journal-title":"Annu. Rev. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1152\/physrev.1997.77.1.51","article-title":"Molecular physiology of vertebrate Na+\/H+ exchangers","volume":"77","author":"Wakabayashi","year":"1997","journal-title":"Physiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1172\/JCI116933","article-title":"Na+\/H+ exchangers, NHE-1 and NHE-3, of rat intestin. Expression and localization","volume":"93","author":"Bookstein","year":"1994","journal-title":"J. Clin. Invest."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1002\/j.1460-2075.1991.tb07725.x","article-title":"Molecular cloning and expression of a cDNA encoding the rabbit ileal villus cell basolateral membrane Na+\/H+ exchanger","volume":"10","author":"Tse","year":"1991","journal-title":"EMBO J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3938","DOI":"10.1073\/pnas.90.9.3938","article-title":"Molecular cloning, sequencing, tissue distribution, and functional expression of a Na+\/H+ exchanger (NHE-2)","volume":"90","author":"Collins","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"C198","DOI":"10.1152\/ajpcell.1995.269.1.C198","article-title":"Cloning, tissue distribution, and functional analysis of the human Na+\/N+ exchanger isoform, NHE3","volume":"269","author":"Brant","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"C1496","DOI":"10.1152\/ajpcell.1997.273.5.C1496","article-title":"Tissue distribution of Na+\/H+ exchanger isoforms NHE2 and NHE4 in rat intestine and kidney","volume":"273","author":"Bookstein","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"G776","DOI":"10.1152\/ajpgi.00297.2001","article-title":"Intestinal NaCl transport in NHE2 and NHE3 knockout mice","volume":"282","author":"Gawenis","year":"2002","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1159\/000113752","article-title":"Gastrointestinal distribution and kinetic characterization of the sodium-hydrogen exchanger isoform 8 (NHE8)","volume":"21","author":"Xu","year":"2008","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"G36","DOI":"10.1152\/ajpgi.00552.2004","article-title":"Subcloning, localization, and expression of the rat intestinal sodium-hydrogen exchanger isoform 8","volume":"289","author":"Xu","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1242\/jeb.028605","article-title":"NHE3 regulatory complexes","volume":"212","author":"Donowitz","year":"2009","journal-title":"J. Exp. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1073\/pnas.94.7.3010","article-title":"cAMP-mediated inhibition of the epithelial brush border Na+\/H+ exchanger, NHE3, requires an associated regulatory protein","volume":"94","author":"Yun","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1111\/j.1440-1681.2008.04931.x","article-title":"The epithelial brush border Na+\/H+ exchanger NHE3 associates with the actin cytoskeleton by binding to ezrin directly and via PDZ domain-containing Na+\/H+ exchanger regulatory factor (NHERF) proteins","volume":"35","author":"Cha","year":"2008","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_20","first-page":"G73","article-title":"Role of Cl channels in Cl-dependent Na\/H exchange","volume":"276","author":"Rajendran","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11051","DOI":"10.1074\/jbc.270.19.11051","article-title":"Chloride-dependent Na-H exchange.A novel mechanism of sodium transport in colonic crypts","volume":"270","author":"Rajendran","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17236","DOI":"10.1074\/jbc.M011763200","article-title":"Regulatory interaction between the cystic fibrosis transmembrane conductance regulator and HCO3- salvage mechanisms in model systems and the mouse pancreatic duct","volume":"276","author":"Ahn","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1007\/s00424-003-1090-3","article-title":"The SLC26 gene family of multifunctional anion exchangers","volume":"447","author":"Mount","year":"2004","journal-title":"Pflugers Arch."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"G573","DOI":"10.1152\/ajpgi.00338.2001","article-title":"Identification of an apical Cl(-)\/HCO3(-) exchanger in the small intestine","volume":"282","author":"Wang","year":"2002","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"G1079","DOI":"10.1152\/ajpgi.00354.2006","article-title":"PAT-1 (Slc26a6) is the predominant apical membrane Cl-\/HCO3- exchanger in the upper villous epithelium of the murine duodenum","volume":"292","author":"Simpson","year":"2007","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"F826","DOI":"10.1152\/ajprenal.00079.2002","article-title":"Molecular characterization of the murine Slc26a6 anion exchanger: Functional comparison with Slc26a1","volume":"283","author":"Xie","year":"2002","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5662","DOI":"10.1093\/emboj\/cdf580","article-title":"A molecular mechanism for aberrant CFTR-dependent HCO(3)(-) transport in cystic fibrosis","volume":"21","author":"Ko","year":"2002","journal-title":"EMBO J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/ng1196-316","article-title":"Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea","volume":"14","author":"Hoglund","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1002\/humu.10139","article-title":"SLC26A3 mutations in congenital chloride diarrhea","volume":"20","author":"Makela","year":"2002","journal-title":"Hum. Mutat."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1053\/j.gastro.2008.11.016","article-title":"Role of down-regulated in adenoma anion exchanger in HCO3- secretion across murine duodenum","volume":"136","author":"Walker","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19744","DOI":"10.1074\/jbc.M109.004127","article-title":"Intestinal anion exchanger down-regulated in adenoma (DRA) is inhibited by intracellular calcium","volume":"284","author":"Lamprecht","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1053\/gast.2002.31875","article-title":"Down-regulated in adenoma mediates apical Cl-\/HCO3- exchange in rabbit, rat, and human duodenum","volume":"122","author":"Jacob","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1053\/j.gastro.2008.07.083","article-title":"Down-regulated in adenoma Cl\/HCO3 exchanger couples with Na\/H exchanger 3 for NaCl absorption in murine small intestine","volume":"135","author":"Walker","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"C1062","DOI":"10.1152\/ajpcell.00454.2003","article-title":"Acid-base effects on intestinal Cl- absorption and vesicular trafficking","volume":"286","author":"Charney","year":"2004","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"G931","DOI":"10.1152\/ajpgi.2000.279.5.G931","article-title":"Regulation of DRA and AE1 in rat colon by dietary Na depletion","volume":"279","author":"Rajendran","year":"2000","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0005-2736(00)00366-7","article-title":"Human intestinal anion exchanger isoforms: Expression, distribution, and membrane localization","volume":"1511","author":"Alrefai","year":"2001","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"G1225","DOI":"10.1152\/ajpgi.00236.2003","article-title":"Identification of an apical Cl-\/HCO3- exchanger in gastric surface mucous and duodenal villus cells","volume":"285","author":"Xu","year":"2003","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/367463a0","article-title":"Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits","volume":"367","author":"Canessa","year":"1994","journal-title":"Nature"},{"key":"ref_39","first-page":"G571","article-title":"Molecular biology of Na+ absorption","volume":"273","author":"Barbry","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.gassur.2004.05.017","article-title":"Comparative study of epithelial gene expression in the small intestine among total proctocolectomized, dietary sodium-depleted, and aldosterone-infused rats","volume":"9","author":"Fukushima","year":"2005","journal-title":"J. Gastrointest. Surg."},{"key":"ref_41","first-page":"G133","article-title":"Amiloride-sensitive salt and fluid absorption in small intestine of sodium-depleted rats","volume":"248","author":"Will","year":"1985","journal-title":"Am. J. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1039\/B810471A","article-title":"Assessment of the CFTR and ENaC association","volume":"5","author":"Berdiev","year":"2009","journal-title":"Mol. Biosyst."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1093\/embo-reports\/kve232","article-title":"The cystic fibrosis transmembrane conductance regulator (CFTR) inhibits ENaC through an increase in the intracellular Cl- concentration","volume":"2","author":"Konig","year":"2001","journal-title":"EMBO Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1113\/jphysiol.2004.079046","article-title":"CFTR fails to inhibit the epithelial sodium channel ENaC expressed in Xenopus laevis oocytes","volume":"564","author":"Nagel","year":"2005","journal-title":"J. Physiol."},{"key":"ref_45","first-page":"G709","article-title":"CFTR-mediated inhibition of epithelial Na+ conductance in human colon is defective in cystic fibrosis","volume":"277","author":"Mall","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/330379a0","article-title":"Expression cloning and cDNA sequencing of the Na+\/glucose co-transporter","volume":"330","author":"Hediger","year":"1987","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1365-2796.2006.01746.x","article-title":"Active sugar transport in health and disease","volume":"261","author":"Wright","year":"2007","journal-title":"J. Intern. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1016\/S0006-3495(95)80110-4","article-title":"Thermodynamic determination of the Na+: Glucose coupling ratio for the human SGLT1 cotransporter","volume":"69","author":"Chen","year":"1995","journal-title":"Biophys. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1056\/NEJM196807252790402","article-title":"Decrease in net stool output in cholera during intestinal perfusion with glucose-containing solutions","volume":"279","author":"Hirschhorn","year":"1968","journal-title":"N. Engl. J. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/350354a0","article-title":"Glucose\/galactose malabsorption caused by a defect in the Na+\/glucose cotransporter","volume":"350","author":"Turk","year":"1991","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2215\/CJN.04010609","article-title":"Familial renal glucosuria and SGLT2: From a mendelian trait to a therapeutic target","volume":"5","author":"Santer","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1152\/physrev.00018.2006","article-title":"Amino acid transport across mammalian intestinal and renal epithelia","volume":"88","author":"Broer","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1126\/science.2475911","article-title":"Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA","volume":"245","author":"Riordan","year":"1989","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/0016-5085(95)90198-1","article-title":"A unique subset of rat and human intestinal villus cells express the cystic fibrosis transmembrane conductance regulator","volume":"108","author":"Ameen","year":"1995","journal-title":"Gastroenterology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1152\/physrev.1999.79.1.S23","article-title":"Structure and function of the CFTR chloride channel","volume":"79","author":"Sheppard","year":"1999","journal-title":"Physiol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1002\/j.1460-2075.1994.tb06355.x","article-title":"Activation of intestinal CFTR Cl- channel by heat-stable enterotoxin and guanylin via cAMP-dependent protein kinase","volume":"13","author":"Chao","year":"1994","journal-title":"EMBO J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/0092-8674(91)90446-6","article-title":"Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel","volume":"66","author":"Cheng","year":"1991","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4978","DOI":"10.1074\/jbc.272.8.4978","article-title":"Phosphorylation by protein kinase C is required for acute activation of cystic fibrosis transmembrane conductance regulator by protein kinase A","volume":"272","author":"Jia","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/352628a0","article-title":"Phosphorylation-regulated Cl- channel in CHO cells stably expressing the cystic fibrosis gene","volume":"352","author":"Tabcharani","year":"1991","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4195","DOI":"10.1074\/jbc.272.7.4195","article-title":"cGMP stimulation of cystic fibrosis transmembrane conductance regulator Cl- channels co-expressed with cGMP-dependent protein kinase type II but not type Ibeta","volume":"272","author":"Vaandrager","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/349793a0","article-title":"Activation of chloride channels in normal and cystic fibrosis airway epithelial cells by multifunctional calcium\/calmodulin-dependent protein kinase","volume":"349","author":"Wagner","year":"1991","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.1016\/S0006-3495(96)79501-2","article-title":"The tyrosine kinase p60c-src regulates the fast gate of the cystic fibrosis transmembrane conductance regulator chloride channel","volume":"71","author":"Fischer","year":"1996","journal-title":"Biophys. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"C375","DOI":"10.1152\/ajpcell.2000.279.2.C375","article-title":"Forskolin-induced apical membrane insertion of virally expressed, epitope-tagged CFTR in polarized MDCK cells","volume":"279","author":"Howard","year":"2000","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"28401","DOI":"10.1074\/jbc.M800516200","article-title":"Regulation of CFTR trafficking by its R domain","volume":"283","author":"Lewarchik","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1126\/science.1373908","article-title":"Regulation of plasma membrane recycling by CFTR","volume":"256","author":"Bradbury","year":"1992","journal-title":"Science"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"C1","DOI":"10.1152\/ajpcell.00554.2002","article-title":"The role of regulated CFTR trafficking in epithelial secretion","volume":"285","author":"Bertrand","year":"2003","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_67","first-page":"731","article-title":"Gastrointestinal manifestations in cystic fibrosis","volume":"8","author":"Eggermont","year":"1996","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_68","first-page":"G258","article-title":"Intestinal physiology and pathology in gene-targeted mouse models of cystic fibrosis","volume":"273","author":"Grubb","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1126\/science.257.5073.1125","article-title":"Defective epithelial chloride transport in a gene-targeted mouse model of cystic fibrosis","volume":"257","author":"Clarke","year":"1992","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/ng0593-35","article-title":"Production of a severe cystic fibrosis mutation in mice by gene targeting","volume":"4","author":"Ratcliff","year":"1993","journal-title":"Nat. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1053\/gast.2000.8524","article-title":"Residual chloride secretion in intestinal tissue of deltaF508 homozygous twins and siblings with cystic fibrosis.The European CF Twin and Sibling Study Consortium","volume":"119","author":"Bronsveld","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"C958","DOI":"10.1152\/ajpcell.1998.274.4.C958","article-title":"Inhibition of Ca(2+)-dependent Cl- secretion in T84 cells: Membrane target(s) of inhibition is agonist specific","volume":"274","author":"Barrett","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/j.1476-5381.1993.tb13599.x","article-title":"Activation by calcium alone of chloride secretion in T84 epithelial cells","volume":"109","author":"Kachintorn","year":"1993","journal-title":"Br. J. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0167-4889(94)90144-9","article-title":"Carbachol stimulates Cl- secretion via activation of two distinct apical Cl- pathways in cultured human T84 intestinal epithelial monolayers","volume":"1220","author":"McEwan","year":"1994","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"6785","DOI":"10.1073\/pnas.89.15.6785","article-title":"Antisense oligodeoxynucleotides to the cystic fibrosis transmembrane conductance regulator inhibit cAMP-activated but not calcium-activated chloride currents","volume":"89","author":"Wagner","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1096\/fasebj.2.10.2838365","article-title":"Altered intestinal chloride transport in cystic fibrosis","volume":"2","author":"Berschneider","year":"1988","journal-title":"FASEB J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1136\/gut.32.9.1035","article-title":"Failure of cholinergic stimulation to induce a secretory response from the rectal mucosa in cystic fibrosis","volume":"32","author":"Hardcastle","year":"1991","journal-title":"Gut"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1136\/gut.29.7.957","article-title":"Failure to induce secretion in jejunal biopsies from children with cystic fibrosis","volume":"29","author":"Taylor","year":"1988","journal-title":"Gut"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/ng0396-280","article-title":"Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor","volume":"12","author":"Rozmahel","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"27205","DOI":"10.1074\/jbc.M504654200","article-title":"hCLCA1 and mCLCA3 are secreted non-integral membrane proteins and therefore are not ion channels","volume":"280","author":"Gibson","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"22461","DOI":"10.1074\/jbc.M313813200","article-title":"A novel human Cl(-) channel family related to Drosophila flightless locus","volume":"279","author":"Suzuki","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"12929","DOI":"10.1073\/pnas.0604505103","article-title":"Bestrophin-2 is a candidate calcium-activated chloride channel involved in olfactory transduction","volume":"103","author":"Pifferi","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1113\/expphysiol.2005.031773","article-title":"The Drosophila tweety family: Molecular candidates for large-conductance Ca2+-activated Cl- channels","volume":"91","author":"Suzuki","year":"2006","journal-title":"Exp. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1126\/science.1163518","article-title":"TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity","volume":"322","author":"Caputo","year":"2008","journal-title":"Science"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1038\/nature07313","article-title":"TMEM16A confers receptor-activated calcium-dependent chloride conductance","volume":"455","author":"Yang","year":"2008","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.cell.2008.09.003","article-title":"Expression cloning of TMEM16A as a calcium-activated chloride channel subunit","volume":"134","author":"Schroeder","year":"2008","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"28698","DOI":"10.1074\/jbc.M109.012120","article-title":"Loss of TMEM16A causes a defect in epithelial Ca2+-dependent chloride transport","volume":"284","author":"Ousingsawat","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"S103","DOI":"10.1007\/s004240100654","article-title":"Non-CFTR chloride channels likely contribute to secretion in the murine small intestine","volume":"443","author":"Gyomorey","year":"2001","journal-title":"Pflugers Arch."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"C1787","DOI":"10.1152\/ajpcell.2000.279.6.C1787","article-title":"Expression of the chloride channel ClC-2 in the murine small intestine epithelium","volume":"279","author":"Gyomorey","year":"2000","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"22276","DOI":"10.1074\/jbc.M309899200","article-title":"Additional disruption of the ClC-2 Cl(-) channel does not exacerbate the cystic fibrosis phenotype of cystic fibrosis transmembrane conductance regulator mouse models","volume":"279","author":"Zdebik","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"C805","DOI":"10.1152\/ajpcell.00291.2001","article-title":"Distribution of ClC-2 chloride channel in rat and human epithelial tissues","volume":"282","author":"Lipecka","year":"2002","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1053\/j.gastro.2009.05.037","article-title":"Activation of intestinal Cl- secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator","volume":"137","author":"Bijvelds","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_93","first-page":"370","article-title":"Prevalence of enterotoxigenic Escherichia coli-associated diarrhoea and carrier state in the developing world","volume":"22","author":"Wenneras","year":"2004","journal-title":"J. Health Popul. Nutr."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1086\/517826","article-title":"Enteroaggregative Escherichia coli strains as a cause of traveler's diarrhea: A case-control study","volume":"177","author":"Gascon","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1128\/CMR.18.3.465-483.2005","article-title":"Enterotoxigenic Escherichia coli in developing countries: Epidemiology, microbiology, clinical features, treatment, and prevention","volume":"18","author":"Qadri","year":"2005","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1086\/338834","article-title":"Prevalence of enteric pathogens among international travelers with diarrhea acquired in Kenya (Mombasa), India (Goa), or Jamaica (Montego Bay)","volume":"185","author":"Jiang","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1128\/CMR.11.1.142","article-title":"Diarrheagenic Escherichia coli","volume":"11","author":"Nataro","year":"1998","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1128\/jb.159.3.1086-1089.1984","article-title":"Vibrio cholerae enterotoxin genes: Nucleotide sequence analysis of DNA encoding ADP-ribosyltransferase","volume":"159","author":"Lockman","year":"1984","journal-title":"J. Bacteriol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1006\/jmbi.1995.0456","article-title":"The three-dimensional crystal structure of cholera toxin","volume":"251","author":"Zhang","year":"1995","journal-title":"J. Mol. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/351371a0","article-title":"Crystal structure of a cholera toxin-related heat-labile enterotoxin from E coli","volume":"351","author":"Sixma","year":"1991","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1006\/jmbi.1993.1209","article-title":"Refined structure of Escherichia coli heat-labile enterotoxin, a close relative of cholera toxin","volume":"230","author":"Sixma","year":"1993","journal-title":"J. Mol. Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1128\/mr.60.1.167-215.1996","article-title":"Enteric bacterial toxins: Mechanisms of action and linkage to intestinal secretion","volume":"60","author":"Sears","year":"1996","journal-title":"Microbiol. Rev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.1432-1033.1982.tb07047.x","article-title":"Amino-acid sequence of a heat-stable enterotoxin produced by human enterotoxigenic Escherichia coli","volume":"129","author":"Aimoto","year":"1982","journal-title":"Eur. J. Biochem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5934","DOI":"10.1016\/S0021-9258(19)67688-X","article-title":"Molecular structure of the toxin domain of heat-stable enterotoxin produced by a pathogenic strain of Escherichia coli. A putative binding site for a binding protein on rat intestinal epithelial cell membranes","volume":"266","author":"Ozaki","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1002\/pro.5560040907","article-title":"The structure of Escherichia coli heat-stable enterotoxin b by nuclear magnetic resonance and circular dichroism","volume":"4","author":"Sukumar","year":"1995","journal-title":"Protein Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1128\/iai.47.3.834-836.1985","article-title":"Revised amino acid sequence for a heat-stable enterotoxin produced by an Escherichia coli strain (18D) that is pathogenic for humans","volume":"47","author":"Thompson","year":"1985","journal-title":"Infect. Immun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1128\/iai.42.2.539-548.1983","article-title":"Chemical properties of heat-stable enterotoxins produced by enterotoxigenic Escherichia coli of different host origins","volume":"42","author":"Dreyfus","year":"1983","journal-title":"Infect. Immun."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"8907","DOI":"10.1073\/pnas.84.24.8907","article-title":"Importance of disulfide bridges in the structure and activity of Escherichia coli enterotoxin ST1b","volume":"84","author":"Gariepy","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1128\/iai.55.9.2121-2125.1987","article-title":"Substitutions of cysteine residues of Escherichia coli heat-stable enterotoxin by oligonucleotide-directed mutagenesis","volume":"55","author":"Okamoto","year":"1987","journal-title":"Infect. Immun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/0014-5793(85)81129-7","article-title":"Essential structure for full enterotoxigenic activity of heat-stable enterotoxin produced by enterotoxigenic Escherichia coli","volume":"181","author":"Yoshimura","year":"1985","journal-title":"FEBS Lett."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/0014-5793(85)80163-0","article-title":"Amino acid sequence of heat-stable enterotoxin produced by Vibrio cholerae non-01","volume":"193","author":"Takao","year":"1985","journal-title":"FEBS Lett."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1432-1033.1985.tb09183.x","article-title":"Isolation, primary structure and synthesis of heat-stable enterotoxin produced by Yersinia enterocolitica","volume":"152","author":"Takao","year":"1985","journal-title":"Eur. J. Biochem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0014-5793(93)81766-S","article-title":"Purification and sequence determination of heat-stable enterotoxin elaborated by a cholera toxin-producing strain of Vibrio cholerae O1","volume":"326","author":"Yoshino","year":"1993","journal-title":"FEBS Lett."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0016-5085(88)90423-4","article-title":"Age-related differences in receptors for Escherichia coli heat-stable enterotoxin in the small and large intestine of children","volume":"94","author":"Cohen","year":"1988","journal-title":"Gastroenterology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/0092-8674(90)90497-3","article-title":"Guanylyl cyclase is a heat-stable enterotoxin receptor","volume":"63","author":"Schulz","year":"1990","journal-title":"Cell"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"17912","DOI":"10.1016\/S0021-9258(18)55214-5","article-title":"Primary structure and functional expression of the human receptor for Escherichia coli heat-stable enterotoxin","volume":"266","author":"Camerato","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1073\/pnas.75.6.2800","article-title":"Heat-stable enterotoxin of Escherichia coli: In vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine","volume":"75","author":"Field","year":"1978","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1126\/science.274.5295.2082","article-title":"Intestinal secretory defects and dwarfism in mice lacking cGMP-dependent protein kinase II","volume":"274","author":"Pfeifer","year":"1996","journal-title":"Science"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"16642","DOI":"10.1074\/jbc.M500505200","article-title":"cGMP inhibition of Na+\/H+ antiporter 3 (NHE3) requires PDZ domain adapter NHERF2, a broad specificity protein kinase G-anchoring protein","volume":"280","author":"Cha","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"26626","DOI":"10.1074\/jbc.270.44.26626","article-title":"Isotype-specific activation of cystic fibrosis transmembrane conductance regulator-chloride channels by cGMP-dependent protein kinase II","volume":"270","author":"French","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/S0960-9822(95)00232-6","article-title":"Identification and partial characterization of a domain in CFTR that may bind cyclic nucleotides directly","volume":"5","author":"Sullivan","year":"1995","journal-title":"Curr. Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1476-5381.1994.tb13024.x","article-title":"Chloride secretion in response to guanylin in colonic epithelial from normal and transgenic cystic fibrosis mice","volume":"112","author":"Cuthbert","year":"1994","journal-title":"Br. J. Pharmacol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/0016-5085(94)90218-6","article-title":"Escherichia coli heat-stable enterotoxin-mediated colonic Cl- secretion is absent in cystic fibrosis","volume":"107","author":"Goldstein","year":"1994","journal-title":"Gastroenterology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"5144","DOI":"10.1128\/iai.64.12.5144-5150.1996","article-title":"Identification of ligand recognition sites in heat-stable enterotoxin receptor, membrane-associated guanylyl cyclase C by site-directed mutational analysis","volume":"64","author":"Wada","year":"1996","journal-title":"Infect. Immun."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"31713","DOI":"10.1074\/jbc.274.44.31713","article-title":"Determination of the binding site on the extracellular domain of guanylyl cyclase C to heat-stable enterotoxin","volume":"274","author":"Hasegawa","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"4803","DOI":"10.1021\/bi00233a023","article-title":"Structural characterization of functionally important regions of the Escherichia coli heat-stable enterotoxin STIb","volume":"30","author":"Carpick","year":"1991","journal-title":"Biochemistry"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1399-3011.2005.00218.x","article-title":"Recognition and signal transduction mechanism of Escherichia coli heat-stable enterotoxin and its receptor, guanylate cyclase C","volume":"65","author":"Hasegawa","year":"2005","journal-title":"J. Pept. Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1128\/iai.57.8.2420-2424.1989","article-title":"Influence of a glycine or proline substitution on the functional properties of a 14-amino-acid analog of Escherichia coli heat-stable enterotoxin","volume":"57","author":"Waldman","year":"1989","journal-title":"Infect. Immun."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1246\/bcsj.63.2063","article-title":"Structure-activity relationship of Escherichia coli heat-stable enterotoxin: Role of Ala residue at position 14 in toxin-receptor interaction","volume":"63","author":"Yamasaki","year":"1990","journal-title":"Bull Chem. Soc. Jpn."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1006\/bbrc.1997.7487","article-title":"Mice lacking the guanylyl cyclase C receptor are resistant to STa-induced intestinal secretion","volume":"239","author":"Mann","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1172\/JCI119683","article-title":"Disruption of the guanylyl cyclase-C gene leads to a paradoxical phenotype of viable but heat-stable enterotoxin-resistant mice","volume":"100","author":"Schulz","year":"1997","journal-title":"J. Clin. Invest."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1073\/pnas.89.3.947","article-title":"Guanylin: An endogenous activator of intestinal guanylate cyclase","volume":"89","author":"Currie","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"9089","DOI":"10.1073\/pnas.89.19.9089","article-title":"Precursor structure, expression, and tissue distribution of human guanylin","volume":"89","author":"Keshav","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s005350170106","article-title":"Guanylin family: New intestinal peptides regulating electrolyte and water homeostasis","volume":"36","author":"Nakazato","year":"2001","journal-title":"J. Gastroenterol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1172\/JCI200318743","article-title":"Uroguanylin knockout mice have increased blood pressure and impaired natriuretic response to enteral NaCl load","volume":"112","author":"Lorenz","year":"2003","journal-title":"J. Clin. Invest."},{"key":"ref_136","first-page":"G633","article-title":"Regulation of intestinal Cl- and HCO3-secretion by uroguanylin","volume":"274","author":"Joo","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"13581","DOI":"10.1021\/bi00250a010","article-title":"Determination of the solution structure of the peptide hormone guanylin: Observation of a novel form of topological stereoisomerism","volume":"33","author":"Skelton","year":"1994","journal-title":"Biochemistry"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1006\/jmbi.2001.4922","article-title":"Structural insights into the ligand binding domains of membrane bound guanylyl cyclases and natriuretic peptide receptors","volume":"311","year":"2001","journal-title":"J. Mol. Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1053\/j.gastro.2007.06.067","article-title":"Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome","volume":"133","author":"Andresen","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1053\/j.gastro.2009.12.050","article-title":"Efficacy of linaclotide for patients with chronic constipation","volume":"138","author":"Lembo","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0005-2736(93)90224-N","article-title":"A 56 kDa binding protein for Escherichia coli heat-stable enterotoxin isolated from the cytoskeleton of rat intestinal membrane does not possess guanylate cyclase activity","volume":"1152","author":"Hakki","year":"1993","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"10738","DOI":"10.1021\/bi00108a019","article-title":"Identification and characterization of a new family of high-affinity receptors for Escherichia coli heat-stable enterotoxin in rat intestinal membranes","volume":"30","author":"Hugues","year":"1991","journal-title":"Biochemistry"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1128\/iai.58.6.1817-1820.1990","article-title":"Heterogeneity of intestinal receptors for Escherichia coli heat-stable enterotoxin","volume":"58","author":"Ivens","year":"1990","journal-title":"Infect. Immun."},{"key":"ref_144","first-page":"G172","article-title":"Comparison of receptors for Escherichia coli heat-stable enterotoxin: Novel receptor present in IEC-6 cells","volume":"264","author":"Mann","year":"1993","journal-title":"Am. J. Physiol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1096\/fj.06-7540com","article-title":"Heat-stable enterotoxin of Escherichia coli (STa) can stimulate duodenal HCO3(-) secretion via a novel GC-C- and CFTR-independent pathway","volume":"22","author":"Sellers","year":"2008","journal-title":"FASEB J."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"G654","DOI":"10.1152\/ajpgi.00386.2004","article-title":"Heat-stable enterotoxin of Escherichia coli stimulates a non-CFTR-mediated duodenal bicarbonate secretory pathway","volume":"288","author":"Sellers","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/j.1469-7793.1997.411bb.x","article-title":"A functional CFTR protein is required for mouse intestinal cAMP-, cGMP- and Ca(2+)-dependent HCO3- secretion","volume":"505","author":"Seidler","year":"1997","journal-title":"J. Physiol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"8440","DOI":"10.1073\/pnas.0803096105","article-title":"Pyridopyrimidine derivatives as inhibitors of cyclic nucleotide synthesis: Application for treatment of diarrhea","volume":"105","author":"Kots","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1016\/j.bmcl.2009.04.024","article-title":"Novel pyridopyrimidine derivatives as inhibitors of stable toxin a (STa) induced cGMP synthesis","volume":"19","author":"Tanifum","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1074\/jbc.272.2.754","article-title":"Interruption of Escherichia coli heat-stable enterotoxin-induced guanylyl cyclase signaling and associated chloride current in human intestinal cells by 2-chloroadenosine","volume":"272","author":"Parkinson","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1096\/fasebj.13.8.913","article-title":"Interruption of transmembrane signaling as a novel antisecretory strategy to treat enterotoxigenic diarrhea","volume":"13","author":"Zhang","year":"1999","journal-title":"FASEB J."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"8247","DOI":"10.1021\/bi036234n","article-title":"Tyrphostins are inhibitors of guanylyl and adenylyl cyclases","volume":"43","author":"Jaleel","year":"2004","journal-title":"Biochemistry"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1053\/j.gastro.2003.11.005","article-title":"Prevention of toxin-induced intestinal ion and fluid secretion by a small-molecule CFTR inhibitor","volume":"126","author":"Thiagarajah","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0016-5085(03)00884-9","article-title":"Diarrhea caused by enterotoxigenic Escherichia coli infection of humans is inhibited by dietary calcium","volume":"125","author":"Witteman","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_155","unstructured":"(2009). Cholera: Global surveillance summary, 2008. Wkly Epidemiol. Rec. , 84, 309\u2013324."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0140-6736(03)15328-7","article-title":"Cholera","volume":"363","author":"Sack","year":"2004","journal-title":"Lancet"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1128\/IAI.01286-07","article-title":"Attenuated endocytosis and toxicity of a mutant cholera toxin with decreased ability to cluster ganglioside GM1 molecules","volume":"76","author":"Wolf","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1574-6968.2006.00545.x","article-title":"Rafting with cholera toxin: Endocytosis and trafficking from plasma membrane to ER","volume":"266","author":"Chinnapen","year":"2007","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.bbamcr.2005.07.007","article-title":"Raft trafficking of AB5 subunit bacterial toxins","volume":"1746","author":"Lencer","year":"2005","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"C1453","DOI":"10.1152\/ajpcell.00189.2004","article-title":"Trafficking of cholera toxin-ganglioside GM1 complex into Golgi and induction of toxicity depend on actin cytoskeleton","volume":"287","author":"Badizadegan","year":"2004","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1172\/JCI106874","article-title":"Effect of cholera enterotoxin on ion transport across isolated ileal mucosa","volume":"51","author":"Field","year":"1972","journal-title":"J. Clin. Invest."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/229266a0","article-title":"Stimulation of intestinal adenyl cyclase by cholera toxin","volume":"229","author":"Sharp","year":"1971","journal-title":"Nature"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1073\/pnas.74.8.3307","article-title":"Mechanism of adenylate cyclase activation by cholera toxin: Inhibition of GTP hydrolysis at the regulatory site","volume":"74","author":"Cassel","year":"1977","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"21907","DOI":"10.1016\/S0021-9258(20)88271-4","article-title":"Mutations of GS alpha designed to alter the reactivity of the protein with bacterial toxins. Substitutions at ARG187 result in loss of GTPase activity","volume":"264","author":"Freissmuth","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/S0021-9258(17)43512-5","article-title":"Amino acid sequence of retinal transducin at the site ADP-ribosylated by cholera toxin","volume":"259","author":"Tsubokawa","year":"1984","journal-title":"J. Biol. Chem."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"5534","DOI":"10.1128\/MCB.00302-07","article-title":"Enhanced sensitivity to cholera toxin in ADP-ribosylarginine hydrolase-deficient mice","volume":"27","author":"Kato","year":"2007","journal-title":"Mol. Cell Biol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"6249","DOI":"10.1073\/pnas.88.14.6249","article-title":"Mechanism of intestinal secretion: Effect of cyclic AMP on rabbit ileal crypt and villus cells","volume":"88","author":"Sundaram","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"G857","DOI":"10.1152\/ajpgi.00462.2006","article-title":"Differential regulation of cholera toxin-inhibited Na-H exchange isoforms by butyrate in rat ileum","volume":"293","author":"Subramanya","year":"2007","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1136\/gut.39.4.528","article-title":"5-hydroxytryptamine release into human jejunum by cholera toxin","volume":"39","author":"Bearcroft","year":"1996","journal-title":"Gut"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/0016-5085(89)91560-6","article-title":"Involvement of 5-hydroxytryptamine, prostaglandin E2, and cyclic adenosine monophosphate in cholera toxin-induced fluid secretion in the small intestine of the rat in vivo","volume":"96","author":"Beubler","year":"1989","journal-title":"Gastroenterology"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1172\/JCI115056","article-title":"Mechanism of intestinal secretion. Effect of serotonin on rabbit ileal crypt and villus cells","volume":"87","author":"Sundaram","year":"1991","journal-title":"J. Clin. Invest."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/sj.bjp.0703414","article-title":"The inhibition of cholera toxin-induced 5-HT release by the 5-HT(3) receptor antagonist, granisetron, in the rat","volume":"130","author":"Turvill","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"4637","DOI":"10.1128\/iai.61.11.4637-4644.1993","article-title":"Enhancing effect of cholera toxin on interleukin-6 secretion by IEC-6 intestinal epithelial cells: Mode of action and augmenting effect of inflammatory cytokines","volume":"61","author":"McGee","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/978-1-4615-1941-6_47","article-title":"The regulation of IL-6 secretion from IEC-6 intestinal epithelial cells by cytokines and mucosally important antigens","volume":"371A","author":"McGee","year":"1995","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"5595","DOI":"10.1128\/IAI.73.9.5595-5602.2005","article-title":"Cholera toxin induces a transient depletion of CD8+ intraepithelial lymphocytes in the rat small intestine as detected by microarray and immunohistochemistry","volume":"73","author":"Flach","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.4049\/jimmunol.154.3.1032","article-title":"Morphologic and functional alterations of mucosal T cells by cholera toxin and its B subunit","volume":"154","author":"Elson","year":"1995","journal-title":"J. Immunol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1128\/IAI.01900-06","article-title":"Broad up-regulation of innate defense factors during acute cholera","volume":"75","author":"Flach","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1126\/science.2549637","article-title":"Role of prostaglandins and cAMP in the secretory effects of cholera toxin","volume":"245","author":"Peterson","year":"1989","journal-title":"Science"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/0016-5085(89)91689-2","article-title":"Comparative study of Clostridium difficile toxin A and cholera toxin in rabbit ileum","volume":"97","author":"Triadafilopoulos","year":"1989","journal-title":"Gastroenterology"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1128\/iai.63.4.1452-1461.1995","article-title":"Comparison of the mechanisms of action of cholera toxin and the heat-stable enterotoxins of Escherichia coli","volume":"63","author":"Peterson","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/BF01071191","article-title":"Prostaglandin E in cholera toxin-induced intestinal secretion. Lack of an intermediary role","volume":"20","author":"Hudson","year":"1975","journal-title":"Am. J. Dig. Dis."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"6234","DOI":"10.1128\/IAI.71.11.6234-6242.2003","article-title":"Role of cyclooxygenase enzymes in a murine model of experimental cholera","volume":"71","author":"Popov","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/S0022-3565(24)29618-X","article-title":"Cholera toxin induces prostaglandin synthesis via post-transcriptional activation of cyclooxygenase-2 in the rat jejunum","volume":"297","author":"Beubler","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1099\/00222615-41-1-3","article-title":"Interactions of intestinal mediators in the mode of action of cholera toxin","volume":"41","author":"Peterson","year":"1994","journal-title":"J. Med. Microbiol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1006\/mpat.2002.0502","article-title":"Positive and negative regulation of water channel aquaporins in human small intestine by cholera toxin","volume":"32","author":"Hamabata","year":"2002","journal-title":"Microb. Pathog."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1078\/0171-9335-00210","article-title":"Expression and immunolocalization of the aquaporin-8 water channel in rat gastrointestinal tract","volume":"80","author":"Calamita","year":"2001","journal-title":"Eur. J. Cell Biol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"12147","DOI":"10.1074\/jbc.M009403200","article-title":"The water channel aquaporin-8 is mainly intracellular in rat hepatocytes, and its plasma membrane insertion is stimulated by cyclic AMP","volume":"276","author":"Garcia","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/S0014-5793(04)00139-5","article-title":"Cholera toxin induces expression of ion channels and carriers in rat small intestinal mucosa","volume":"561","author":"Flach","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1016\/j.febslet.2007.06.001","article-title":"Differential expression of intestinal membrane transporters in cholera patients","volume":"581","author":"Flach","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1126\/science.7524148","article-title":"Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model","volume":"266","author":"Gabriel","year":"1994","journal-title":"Science"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1172\/JCI0216112","article-title":"Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion","volume":"110","author":"Ma","year":"2002","journal-title":"J. Clin. Invest."},{"key":"ref_192","first-page":"G58","article-title":"A novel plant-derived inhibitor of cAMP-mediated fluid and chloride secretion","volume":"276","author":"Gabriel","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jep.2004.04.005","article-title":"A novel extract SB-300 from the stem bark latex of Croton lechleri inhibits CFTR-mediated chloride secretion in human colonic epithelial cells","volume":"93","author":"Fischer","year":"2004","journal-title":"J. Ethnopharmacol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1085\/jgp.200409059","article-title":"Discovery of glycine hydrazide pore-occluding CFTR inhibitors: Mechanism, structure-activity analysis, and in vivo efficacy","volume":"124","author":"Muanprasat","year":"2004","journal-title":"J. Gen. Physiol."},{"key":"ref_195","first-page":"197","article-title":"Oral fluid therapy of cholera among Bangladesh refugees","volume":"132","author":"Mahalanabis","year":"1973","journal-title":"Johns Hopkins Med. J."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1056\/NEJMoa054493","article-title":"Single-dose azithromycin for the treatment of cholera in adults","volume":"354","author":"Saha","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s13312-010-0059-5","article-title":"Single Dose Azithromycin Versus Ciprofloxacin for Cholera in Children: A Randomized Controlled Trial","volume":"47","author":"Kaushik","year":"2010","journal-title":"Indian Pediatr."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"988","DOI":"10.3201\/eid1006.030519","article-title":"First report from the Asian Rotavirus Surveillance Network","volume":"10","author":"Bresee","year":"2004","journal-title":"Emerg. Infect. Dis."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1086\/320733","article-title":"The epidemiology and disease burden of rotavirus in Vietnam: Sentinel surveillance at 6 hospitals","volume":"183","author":"Nguyen","year":"2001","journal-title":"J. Infect. Dis."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"304","DOI":"10.3201\/eid1202.050006","article-title":"Rotavirus and severe childhood diarrhea","volume":"12","author":"Parashar","year":"2006","journal-title":"Emerg. Infect. Dis."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1086\/512863","article-title":"Hospitalizations and deaths from diarrhea and rotavirus among children <5 years of age in the United States, 1993-2003","volume":"195","author":"Fischer","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"3960","DOI":"10.1073\/pnas.94.8.3960","article-title":"The rotavirus enterotoxin NSP4 mobilizes intracellular calcium in human intestinal cells by stimulating phospholipase C-mediated inositol 1,4,5-trisphosphate production","volume":"94","author":"Dong","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1126\/science.272.5258.101","article-title":"Age-dependent diarrhea induced by a rotaviral nonstructural glycoprotein","volume":"272","author":"Ball","year":"1996","journal-title":"Science"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1126\/science.287.5452.491","article-title":"Role of the enteric nervous system in the fluid and electrolyte secretion of rotavirus diarrhea","volume":"287","author":"Lundgren","year":"2000","journal-title":"Science"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"4442","DOI":"10.4049\/jimmunol.163.8.4442","article-title":"The epithelial cell response to rotavirus infection","volume":"163","author":"Rollo","year":"1999","journal-title":"J. Immunol."},{"key":"ref_206","first-page":"236","article-title":"An electron microscopic investigation of time-related changes in the intestine of neonatal mice infected with murine rotavirus","volume":"7","author":"Osborne","year":"1988","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"4553","DOI":"10.1128\/jvi.63.11.4553-4562.1989","article-title":"Receptor activity of rotavirus nonstructural glycoprotein NS28","volume":"63","author":"Au","year":"1989","journal-title":"J. Virol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1002\/j.1460-2075.1989.tb03561.x","article-title":"Topology of the non-structural rotavirus receptor glycoprotein NS28 in the rough endoplasmic reticulum","volume":"8","author":"Bergmann","year":"1989","journal-title":"EMBO J."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1128\/JVI.79.1.184-192.2005","article-title":"Silencing the morphogenesis of rotavirus","volume":"79","author":"Lopez","year":"2005","journal-title":"J. Virol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"3935","DOI":"10.1128\/JVI.80.8.3935-3946.2006","article-title":"Dissecting rotavirus particle-raft interaction with small interfering RNAs: Insights into rotavirus transit through the secretory pathway","volume":"80","author":"Cuadras","year":"2006","journal-title":"J. Virol."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"11663","DOI":"10.1128\/JVI.74.24.11663-11670.2000","article-title":"A functional NSP4 enterotoxin peptide secreted from rotavirus-infected cells","volume":"74","author":"Zhang","year":"2000","journal-title":"J. Virol."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"5472","DOI":"10.1128\/JVI.01862-06","article-title":"Full-length, glycosylated NSP4 is localized to plasma membrane caveolae by a novel raft isolation technique","volume":"81","author":"Storey","year":"2007","journal-title":"J. Virol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"12343","DOI":"10.1128\/JVI.01378-06","article-title":"Rotavirus nonstructural glycoprotein NSP4 is secreted from the apical surfaces of polarized epithelial cells","volume":"80","author":"Bugarcic","year":"2006","journal-title":"J. Virol."},{"key":"ref_214","first-page":"G431","article-title":"NSP4 elicits age-dependent diarrhea and Ca(2+)mediated I(-) influx into intestinal crypts of CF mice","volume":"277","author":"Morris","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"11331","DOI":"10.1128\/JVI.00577-08","article-title":"Expression of nonstructural rotavirus protein NSP4 mimics Ca2+ homeostasis changes induced by rotavirus infection in cultured cells","volume":"82","author":"Diaz","year":"2008","journal-title":"J. Virol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"5815","DOI":"10.1128\/JVI.02719-07","article-title":"Silencing of rotavirus NSP4 or VP7 expression reduces alterations in Ca2+ homeostasis induced by infection of cultured cells","volume":"82","author":"Zambrano","year":"2008","journal-title":"J. Virol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1007\/s00705-008-0118-6","article-title":"Early transcriptional response in the jejunum of germ-free piglets after oral infection with virulent rotavirus","volume":"153","author":"Hulst","year":"2008","journal-title":"Arch. Virol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1086\/605125","article-title":"Rotavirus induces a biphasic enterotoxic and cytotoxic response in human-derived intestinal enterocytes, which is inhibited by human immunoglobulins","volume":"200","author":"Bracale","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"9464","DOI":"10.1128\/JVI.74.20.9464-9470.2000","article-title":"Direct inhibitory effect of rotavirus NSP4(114-135) peptide on the Na(+)-D-glucose symporter of rabbit intestinal brush border membrane","volume":"74","author":"Halaihel","year":"2000","journal-title":"J. Virol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1128\/JVI.75.3.1540-1546.2001","article-title":"NSP4 enterotoxin of rotavirus induces paracellular leakage in polarized epithelial cells","volume":"75","author":"Tafazoli","year":"2001","journal-title":"J. Virol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1097\/MOG.0b013e328317c897","article-title":"Rotavirus vaccines and pathogenesis: 2008","volume":"25","author":"Hyser","year":"2009","journal-title":"Curr. Opin. Gastroenterol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/2\/8\/2132\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T22:03:07Z","timestamp":1760220187000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/2\/8\/2132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,8,10]]},"references-count":221,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2010,8]]}},"alternative-id":["toxins2082132"],"URL":"https:\/\/doi.org\/10.3390\/toxins2082132","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,8,10]]}}}