{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T08:40:11Z","timestamp":1778402411965,"version":"3.51.4"},"reference-count":113,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the University of Warmia and Mazury in Olsztyn (statutory research)","award":["15.610.003-300"],"award-info":[{"award-number":["15.610.003-300"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide widely distributed in the central nervous system (CNS) and many peripheral organs, such as the digestive tract, endocrine, reproductive and respiratory systems, where it plays different regulatory functions and exerts a cytoprotective effect. The multifarious physiological effects of PACAP are mediated through binding to different G protein-coupled receptors, including PAC1 (PAC1-R), VPAC1 (VPAC1-R) and VPAC2 (VPAC2-R) receptors. In the gastrointestinal (GI) tract, PACAP plays an important regulatory function. PACAP stimulates the secretion of digestive juices and hormone release, regulates smooth muscle contraction, local blood flow, cell migration and proliferation. Additionally, there are many reports confirming the involvement of PACAP in pathological processes within the GI tract, including inflammatory states, neuronal injury, diabetes, intoxication and neoplastic processes. The purpose of this review is to summarize the distribution and pleiotropic action of PACAP in the control of GI tract function and its cytoprotective effect in the course of GI tract disorders.<\/jats:p>","DOI":"10.3390\/ijms22168682","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T10:54:41Z","timestamp":1628765681000},"page":"8682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Physiological and Pathological Processes within the Gastrointestinal Tract: A Review"],"prefix":"10.3390","volume":"22","author":[{"given":"Aleksandra","family":"Karpiesiuk","sequence":"first","affiliation":[{"name":"Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego Str. 13, 10-718 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7593-9552","authenticated-orcid":false,"given":"Katarzyna","family":"Palus","sequence":"additional","affiliation":[{"name":"Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego Str. 13, 10-718 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/0006-291X(90)92140-U","article-title":"Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38)","volume":"170","author":"Miyata","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"366","DOI":"10.3389\/fnins.2020.00366","article-title":"Tracing the Origins of the Pituitary Adenylate-Cyclase Activating Polypeptide (PACAP)","volume":"14","author":"Cardoso","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/1043-2760(92)90139-R","article-title":"Receptors for pituitary adenylate cyclase-activating polypeptide: Comparison with vasoactive intestinal peptide receptors","volume":"3","author":"Arimura","year":"1992","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1124\/pr.109.001370","article-title":"Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery","volume":"61","author":"Vaudry","year":"2009","journal-title":"Pharmacol. Rev."},{"key":"ref_5","first-page":"269","article-title":"Pituitary adenylate cyclase-activating polypeptide and its receptors: From structure to functions","volume":"52","author":"Vaudry","year":"2000","journal-title":"Pharmacol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Horvath, G., Opper, B., and Reglodi, D. (2019). The Neuropeptide Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is Protective in Inflammation and Oxidative Stress-Induced Damage in the Kidney. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194944"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s004410050980","article-title":"Pituitary adenylate cyclase activating polypeptide (PACAP) in the gastrointestinal tract of the rat: Distribution and effects of capsaicin or denervation","volume":"291","author":"Hannibal","year":"1998","journal-title":"Cell Tissue Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3389\/fendo.2018.00090","article-title":"Presence and Effects of Pituitary Adenylate Cyclase Activating Polypeptide Under Physiological and Pathological Conditions in the Stomach","volume":"9","author":"Reglodi","year":"2018","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0167-0115(99)00024-5","article-title":"Biological relevance of pituitary adenylate cyclase-activating polypeptide (PACAP) in the gastrointestinal tract","volume":"84","author":"Modlin","year":"1999","journal-title":"Regul. Pept."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s12031-012-9838-x","article-title":"Changes in pituitary adenylate cyclase-activating Peptide 27-like immunoreactive nervous structures in the porcine descending colon during selected pathological processes","volume":"48","author":"Gonkowski","year":"2012","journal-title":"J. Mol. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Palus, K., Bulc, M., Ca\u0142ka, J., Zielonka, \u0141., and Nowicki, M. (2021). Diabetes Affects the Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)-Like Immunoreactive Enteric Neurons in the Porcine Digestive Tract. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115727"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1007\/s12031-015-0537-2","article-title":"The Influence of Low Doses of Zearalenone on Distribution of Selected Active Substances in Nerve Fibers Within the Circular Muscle Layer of Porcine Ileum","volume":"56","author":"Gonkowski","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Thoene, M., Rytel, L., Dzika, E., and Wojtkiewicz, J. (2021). Increased PACAP- and D\u03b2H-Positive Hepatic Nerve Fibers after Bisphenol A Exposure. Toxics, 9.","DOI":"10.3390\/toxics9050110"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"208","DOI":"10.2478\/v10042-010-0052-9","article-title":"Changes in vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide and neuropeptide Y-ergic structures of the enteric nervous system in the carcinoma of the human large intestine","volume":"48","author":"Godlewski","year":"2010","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s12031-012-9815-4","article-title":"PACAP immunoreactivity in human malignant tumor samples and cardiac diseases","volume":"48","author":"Szanto","year":"2012","journal-title":"J. Mol. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s004290050189","article-title":"Light and electron microscopic studies of pituitary adenylate cyclase-activating peptide (PACAP)--immunoreactive neurons in the enteric nervous system of rat small and large intestine","volume":"198","author":"Nagahama","year":"1998","journal-title":"Anat. Embryol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.1749-6632.1998.tb11173.x","article-title":"The pituitary adenylate cyclase activating polypeptide type 1 receptor (PAC1-R) is expressed on gastric ECL cells: Evidence by immunocytochemistry and RT-PCR","volume":"865","author":"Zeng","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0167-0115(02)00192-1","article-title":"Distribution of PACAP and its mRNA in several nonneural tissues of rats demonstrated by sandwich enzyme immunoassay and RT-PCR technique","volume":"109","author":"Heinzlmann","year":"2002","journal-title":"Regul. Pept."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/0306-4522(92)90064-9","article-title":"Pituitary adenylate cyclase activating peptide: A novel vasoactive intestinal peptide-like neuropeptide in the gut","volume":"46","author":"Sundler","year":"1992","journal-title":"Neuroscience"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s00424-005-1491-6","article-title":"Roles of PACAP and PHI as inhibitory neurotransmitters in the circular muscle of mouse antrum","volume":"451","author":"Toyoshima","year":"2006","journal-title":"Pfl\u00fcg. Arch."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/BF00318496","article-title":"Distribution of pituitary adenylyl cyclase-activating peptide (PACAP) immunoreactivity in neurons of the guinea-pig digestive tract and their projections in the ileum and colon","volume":"279","author":"Portbury","year":"1995","journal-title":"Cell Tissue Res."},{"key":"ref_22","first-page":"19","article-title":"Immunohistochemical comparison of localization of pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) in the enteric nerve plexus of the guinea pig jejunum","volume":"2","author":"Suzuki","year":"1996","journal-title":"Biomed. Pept. Proteins Nucleic Acids"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s00441-002-0696-7","article-title":"Anatomical and neurochemical features of the extrinsic and intrinsic innervation of the striated muscle in the porcine esophagus: Evidence for regional and species differences","volume":"311","author":"Wu","year":"2003","journal-title":"Cell Tissue Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"179","DOI":"10.5603\/FHC.a2019.0020","article-title":"Increased expression of CART, nNOS, VIP, PACAP, SP and GAL in enteric neurons of the porcine stomach prepyloric region following hydrochloric acid infusion","volume":"57","author":"Calka","year":"2019","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"564457","DOI":"10.3389\/fphar.2020.564457","article-title":"Neurochemistry of Enteric Neurons Following Prolonged Indomethacin Administration in the Porcine Duodenum","volume":"11","author":"Czajkowska","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1007\/s12031-019-01473-y","article-title":"Changes in the Neurochemical Characterization of Enteric Neurons in the Porcine Duodenum after Administration of Low-Dose Salmonella Enteritidis Lipopolysaccharides","volume":"71","author":"Rytel","year":"2020","journal-title":"J. Mol. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/0167-0115(91)90074-Q","article-title":"PACAP, a VIP-like peptide, in neurons of the esophagus","volume":"36","author":"Uddman","year":"1991","journal-title":"Regul. Pept."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/S0196-9781(99)00084-4","article-title":"Pituitary adenylate cyclase activating polypeptide (PACAP) is present in human and cat gastric glands","volume":"20","author":"Vincze","year":"1999","journal-title":"Peptides"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/BF00319630","article-title":"A novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in human intestine: Evidence for reduced content in Hirschsprung\u2019s disease","volume":"269","author":"Shen","year":"1992","journal-title":"Cell Tissue Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"847-e58","DOI":"10.1111\/j.1365-2982.2009.01308.x","article-title":"Post inflammatory damage to the enteric nervous system in diverticular disease and its relationship to symptoms","volume":"21","author":"Simpson","year":"2009","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_31","first-page":"117","article-title":"Analysis of enteral nervous system in children with drug resistant ulcerative colitis","volume":"11","author":"Landowski","year":"2007","journal-title":"Med. Wieku Rozw."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1515\/pjvs-2015-0044","article-title":"Pituitary adenylate cyclase-activating peptide-27 (PACAP-27) is co-stored with galanin, substance P and corticotropin releasing factor (CRF) in intrapancreatic ganglia of the sheep","volume":"18","author":"Arciszewski","year":"2015","journal-title":"Pol. J. Vet. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/0196-9781(93)90131-Y","article-title":"Immunohistochemical localization of PACAP in the ovine digestive system","volume":"14","author":"Arimura","year":"1993","journal-title":"Peptides"},{"key":"ref_34","first-page":"851","article-title":"Immunohistochemical distribution of cocaine- and amphetamine-regulated transcript peptide\u2014Like immunoreactive (CART-LI) nerve fibers and various degree of co-localization with other neuronal factors in the circular muscle layer of human descending colon","volume":"28","author":"Gonkowski","year":"2013","journal-title":"Histol. Histopathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/j.1476-5381.2012.01871.x","article-title":"Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1","volume":"166","author":"Harmar","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"644644","DOI":"10.3389\/fmolb.2021.644644","article-title":"Molecular Basis of Class B GPCR Selectivity for the Neuropeptides PACAP and VIP","volume":"8","author":"Liao","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3389\/fendo.2013.00055","article-title":"Alternative Splicing of the Pituitary Adenylate Cyclase-Activating Polypeptide Receptor PAC1: Mechanisms of Fine Tuning of Brain Activity","volume":"4","author":"Blechman","year":"2013","journal-title":"Front. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1007\/s11064-015-1607-0","article-title":"Pituitary Adenylate Cyclase-Activating Polypeptide Receptors Signal via Phospholipase C Pathway to Block Apoptosis in Newborn Rat Retina","volume":"40","author":"Lakk","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1007\/s12031-020-01769-4","article-title":"PACAP and NAP: Effect of Two Functionally Related Peptides in Diabetic Retinopathy","volume":"71","author":"Maugeri","year":"2021","journal-title":"J. Mol. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.3389\/fnins.2019.01031","article-title":"Neuroprotective Potential of Pituitary Adenylate Cyclase Activating Polypeptide in Retinal Degenerations of Metabolic Origin","volume":"13","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_41","first-page":"199","article-title":"Inhibitory transmission in guinea pig stomach mediated by distinct receptors for pituitary adenylate cyclase-activating peptide","volume":"278","author":"Katsoulis","year":"1996","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S0016-5085(99)70184-8","article-title":"Pituitary adenylate cyclase-activating polypeptide modulates gastric enterochromaffin-like cell proliferation in rats","volume":"116","author":"Modlin","year":"1999","journal-title":"Gastroenterology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/j.1749-6632.1996.tb17512.x","article-title":"Effects of PACAP-VIP hybrid peptides on gastric blood flow in conscious dogs","volume":"805","author":"Naruse","year":"1996","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_44","first-page":"G295","article-title":"PACAP is a stimulator of neurogenic contraction in guinea pig ileum","volume":"265","author":"Katsoulis","year":"1993","journal-title":"Am. J. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/0196-9781(93)90149-B","article-title":"Pituitary adenylate cyclase activating polypeptide (PACAP) is a potent relaxant of the rat ileum","volume":"14","author":"Katsoulis","year":"1993","journal-title":"Peptides"},{"key":"ref_46","first-page":"G217","article-title":"Locations and molecular forms of PACAP and sites and characteristics of PACAP receptors in canine ileum","volume":"274","author":"Mao","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"625","DOI":"10.3109\/00365529309096101","article-title":"Pituitary adenylate cyclase-activating peptide is a potent modulator of human colonic motility","volume":"28","author":"Clemens","year":"1993","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/j.1476-5381.1996.tb15719.x","article-title":"VIP- and PACAP-mediated nonadrenergic, noncholinergic inhibition in longitudinal muscle of rat distal colon: Involvement of activation of charybdotoxin- and apamin-sensitive K+ channels","volume":"119","author":"Kishi","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1210\/endo.139.6.6040","article-title":"Interactive mechanisms among pituitary adenylate cyclase-activating peptide, vasoactive intestinal peptide, and parathyroid hormone receptors in guinea pig cecal circular smooth muscle cells","volume":"139","author":"Motomura","year":"1998","journal-title":"Endocrinology"},{"key":"ref_50","first-page":"511","article-title":"Pituitary adenylate cyclase activating peptide, a novel VIP-like gut-brain peptide, relaxes the guinea-pig taenia caeci via apamin-sensitive potassium channels","volume":"346","author":"Katsoulis","year":"1992","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_51","first-page":"2451","article-title":"Receptors for pituitary adenylate cyclase-activating peptide in human liver","volume":"80","author":"Guijarro","year":"1995","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_52","first-page":"G97","article-title":"PACAP and VIP receptors in rat liver membranes","volume":"260","author":"Robberecht","year":"1991","journal-title":"Am. J. Physiol."},{"key":"ref_53","first-page":"G1433","article-title":"Dual effects of PACAP on guinea pig gallbladder muscle via PACAP-preferring and VIP\/PACAP-preferring receptors","volume":"272","author":"Parkman","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0014-5793(90)80158-F","article-title":"Presence of highly selective receptors for PACAP (pituitary adenylate cyclase activating peptide) in membranes from the rat pancreatic acinar cell line AR 4-2","volume":"262","author":"Buscail","year":"1990","journal-title":"J. FEBS Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8235","DOI":"10.1158\/1078-0432.CCR-04-0939","article-title":"Immunocytochemical identification of VPAC1, VPAC2, and PAC1 receptors in normal and neoplastic human tissues with subtype-specific antibodies","volume":"10","author":"Schulz","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0167-0115(02)00003-4","article-title":"Expression of pituitary adenylate cyclase-activating polypeptide and PACAP type 1 receptor in the rat gastric and colonic myenteric neurons","volume":"105","author":"Miampamba","year":"2002","journal-title":"Regul. Pept."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0304-3835(95)03768-R","article-title":"Differential expression of VIP\/PACAP receptor genes in breast, intestinal, and pancreatic cell lines","volume":"92","author":"Waschek","year":"1995","journal-title":"Cancer Lett."},{"key":"ref_58","first-page":"G769","article-title":"Involvement of pituitary adenylate cyclase-activating peptide in opossum internal anal sphincter relaxation","volume":"275","author":"Chakder","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"G16","DOI":"10.1152\/ajpgi.00081.2017","article-title":"Expression and localization of VPAC1, the major receptor of vasoactive intestinal peptide along the length of the intestine","volume":"313","author":"Jayawardena","year":"2017","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3389\/fncel.2017.00118","article-title":"VPAC Receptor Subtypes Tune Purinergic Neuron-to-Glia Communication in the Murine Submucosal Plexus","volume":"11","author":"Fung","year":"2017","journal-title":"Front. Cell Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1111\/j.1476-5381.1996.tb15256.x","article-title":"Comparative effects of PACAP and VIP on pancreatic endocrine secretions and vascular resistance in rat","volume":"117","author":"Bertrand","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1073\/pnas.91.7.2679","article-title":"Cloning and functional characterization of a third pituitary adenylate cyclase-activating polypeptide receptor subtype expressed in insulin-secreting cells","volume":"91","author":"Inagaki","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","first-page":"G1391","article-title":"Characterization of PACAP receptors and signaling pathways in rabbit gastric muscle cells","volume":"272","author":"Murthy","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0167-0115(98)00112-8","article-title":"Selective expression of vasoactive intestinal peptide (VIP)2\/pituitary adenylate cyclase-activating polypeptide (PACAP)3 receptors in rabbit and guinea pig gastric and tenia coli smooth muscle cells","volume":"77","author":"Teng","year":"1998","journal-title":"Regul. Pept."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0014-2999(98)00662-1","article-title":"Influence of selective VIP receptor agonists in the rat gastric fundus","volume":"359","author":"Robberecht","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1111\/j.1476-5381.1995.tb15939.x","article-title":"Distribution and effects of pituitary adenylate cyclase activating peptide in cat and human lower oesophageal sphincter","volume":"116","author":"Ny","year":"1995","journal-title":"Br. J. Pharmacol."},{"key":"ref_67","first-page":"G901","article-title":"Chief cells possess a receptor with high affinity for PACAP and VIP that stimulates pepsinogen release","volume":"263","author":"Felley","year":"1992","journal-title":"Am. J. Physiol."},{"key":"ref_68","first-page":"53","article-title":"Control of secretion from rat stomach ECL cells in situ and in primary culture","volume":"234","author":"Chen","year":"2001","journal-title":"Scand. J. Clin. Lab. Investig. Suppl."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"G997","DOI":"10.1152\/ajpgi.2001.281.4.G997","article-title":"PACAP stimulates gastric acid secretion in the rat by inducing histamine release","volume":"281","author":"Sandvik","year":"2001","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/sj.bjp.0705739","article-title":"Peripheral PACAP inhibits gastric acid secretion through somatostatin release in mice","volume":"142","author":"Piqueras","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1385\/JMN:26:1:085","article-title":"PACAP regulation of secretion and proliferation of pure populations of gastric ECL cells","volume":"26","author":"Oh","year":"2005","journal-title":"J. Mol. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0167-0115(01)00314-7","article-title":"PACAP mediates the neural proliferative pathway of Mastomys enterochromaffin-like cell transformation","volume":"102","author":"Tang","year":"2001","journal-title":"Regul. Pept."},{"key":"ref_73","first-page":"G303","article-title":"Region-specific antiproliferative effect of VIP and PACAP-(1-38) on rabbit enteric smooth muscle","volume":"276","author":"Depoortere","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/j.1365-2982.2005.00733.x","article-title":"Involvement of M(2) muscarinic receptors in relaxant response of circular muscle of mouse gastric antrum","volume":"18","author":"Takeuchi","year":"2006","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0014-2999(97)01144-8","article-title":"Distinct receptors mediate pituitary adenylate cyclase-activating peptide- and vasoactive intestinal peptide-induced relaxation of rat ileal longitudinal muscle","volume":"334","author":"Ekblad","year":"1997","journal-title":"Eur. J. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0167-0115(98)00046-9","article-title":"Pituitary adenylate cyclase-activating polypeptide (PACAP) induces duodenal phasic contractions via the vagal cholinergic nerves in sheep","volume":"77","author":"Onaga","year":"1998","journal-title":"Regul. Pept."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"102854","DOI":"10.1016\/j.autneu.2021.102854","article-title":"The role of enteric inhibitory neurons in intestinal motility","volume":"235","author":"Costa","year":"2021","journal-title":"Auton. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/j.1476-5381.1992.tb14363.x","article-title":"Pituitary adenylate cyclase activating polypeptides, PACAP-27 and PACAP-38: Stimulators of electrogenic ion secretion in the rat small intestine","volume":"106","author":"Cox","year":"1992","journal-title":"Br. J. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1111\/j.1749-6632.1996.tb17534.x","article-title":"Pituitary adenylate cyclase-activating polypeptide: A potent activator of human intestinal ion transport","volume":"805","author":"Fuchs","year":"1996","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_80","first-page":"G646","article-title":"PACAPs stimulate duodenal bicarbonate secretion at PACAP receptors in the rat","volume":"272","author":"Takeuchi","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_81","first-page":"G516","article-title":"Pituitary adenylate cyclase-activating polypeptide stimulates cholecystokinin secretion in STC-1 cells","volume":"271","author":"Chang","year":"1996","journal-title":"Am. J. Physiol."},{"key":"ref_82","first-page":"83","article-title":"Regulation of 5-HT release from enterochromaffin cells","volume":"73","author":"Reimann","year":"1996","journal-title":"Behav. Brain Res."},{"key":"ref_83","first-page":"G192","article-title":"Modulation of secretin release by neuropeptides in secretin-producing cells","volume":"275","author":"Chang","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/0165-1838(94)00102-P","article-title":"Histochemical, pharmacological, biochemical and chromatographic evidence that pituitary adenylyl cyclase activating peptide is involved in inhibitory neurotransmission in the taenia of the guinea-pig caecum","volume":"50","author":"McConalogue","year":"1995","journal-title":"J. Auton. Nerv. Syst."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0196-9781(94)00143-T","article-title":"PACAP stimulates glucose output from the perfused rat liver","volume":"16","author":"Yokota","year":"1995","journal-title":"Peptides"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/00006676-199401000-00018","article-title":"Comparison between the effects of VIP and the novel peptide PACAP on the exocrine pancreatic secretion of the rat","volume":"9","author":"Alonso","year":"1994","journal-title":"Pancreas"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1097\/00006676-199307000-00012","article-title":"PACAP and VIP stimulate enzyme secretion in rat pancreatic acini via interaction with VIP\/PACAP-2 receptors: Additive augmentation of CCK\/carbachol-induced enzyme release","volume":"8","author":"Schmidt","year":"1993","journal-title":"Pancreas"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1620\/tjem.171.243","article-title":"The stimulatory effects and binding characteristics of PACAP27 in rat dispersed pancreatic acini","volume":"171","author":"Kashimura","year":"1993","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/0196-9781(91)90101-T","article-title":"Effect of pituitary adenylate cyclase activating polypeptide on rat pancreatic exocrine secretion","volume":"12","author":"Mungan","year":"1991","journal-title":"Peptides"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1016\/S0021-9258(17)42256-3","article-title":"Pituitary adenylate cyclase activating polypeptide is an extraordinarily potent intra-pancreatic regulator of insulin secretion from islet beta-cells","volume":"269","author":"Yada","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_91","first-page":"473","article-title":"Stimulatory effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on insulin and glucagon release from the isolated perfused rat pancreas","volume":"129","author":"Yokota","year":"1993","journal-title":"Acta Endocrinol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Heimesaat, M.M., Dunay, I.R., Schulze, S., Fischer, A., Grundmann, U., Alutis, M., K\u00fchl, A.A., Tamas, A., Toth, G., and Dunay, M.P. (2014). Pituitary adenylate cyclase-activating polypeptide ameliorates experimental acute ileitis and extra-intestinal sequelae. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108389"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"554","DOI":"10.3389\/fimmu.2019.00554","article-title":"Pituitary Adenylate Cyclase-Activating Polypeptide-A Neuropeptide as Novel Treatment Option for Subacute Ileitis in Mice Harboring a Human Gut Microbiota","volume":"10","author":"Bereswill","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1007\/s10989-018-9748-z","article-title":"Effect of PACAP on Bacterial Adherence and Cytokine Expression in Intestinal Cell Cultures","volume":"25","author":"Illes","year":"2019","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1556\/1886.2017.00021","article-title":"Intestinal Microbiota Changes in Mice Lacking Pituitary Adenylate Cyclase Activating Polypeptide (PACAP)\u2014Bifidobacteria Make the Difference","volume":"7","author":"Heimesaat","year":"2017","journal-title":"Eur. J. Microbiol. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Kun, J., Szitter, I., Kem\u00e9ny, A., Perkecz, A., Kereskai, L., Poh\u00f3czky, K., Vincze, A., G\u00f3di, S., Szab\u00f3, I., and Szolcs\u00e1nyi, J. (2014). Upregulation of the transient receptor potential ankyrin 1 ion channel in the inflamed human and mouse colon and its protective roles. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108164"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/jcp.21381","article-title":"PACAP provides colonic protection against dextran sodium sulfate induced colitis","volume":"216","author":"Azuma","year":"2008","journal-title":"J. Cell. Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1002\/ijc.23308","article-title":"Induction of colitis and rapid development of colorectal tumors in mice deficient in the neuropeptide PACAP","volume":"122","author":"Nemetz","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Heimesaat, M.M., Mousavi, S., Kl\u00f8ve, S., Genger, C., Weschka, D., Tamas, A., Reglodi, D., and Bereswill, S. (2020). Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute Campylobacter jejuni-induced Enterocolitis in Mice. Pathogens, 9.","DOI":"10.3390\/pathogens9100805"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Reglodi, D., and Tamas, A. (2016). Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide. Pituitary Adenylate Cyclase Activating Polypeptide\u2014PACAP, Current Topics in Neurotoxicity 11, Springer.","DOI":"10.1007\/978-3-319-35135-3"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1556\/maseb.66.2013.5.4","article-title":"[Examination of cytoprotective and anti-inflammatory effect of PACAP-38 on small bowel autotransplantation]","volume":"66","author":"Nedvig","year":"2013","journal-title":"Magy. Seb."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.transproceed.2008.10.084","article-title":"Changes and effect of PACAP-38 on intestinal ischemia-reperfusion and autotransplantation","volume":"41","author":"Ferencz","year":"2009","journal-title":"Transplant. Proc."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1016\/j.transproceed.2010.05.014","article-title":"Comparison of intestinal cold preservation injury on pituitary adenylate cyclase-activating polypeptide in knockout and wild-type mice","volume":"42","author":"Ferencz","year":"2010","journal-title":"Transplant. Proc."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.npep.2017.07.002","article-title":"Effects of pituitary adenylate cyclase activating polypeptide on small intestinal INT 407 cells","volume":"65","author":"Illes","year":"2017","journal-title":"Neuropeptides"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Sadanandan, N., Cozene, B., Park, Y.J., Farooq, J., Kingsbury, C., Wang, Z.J., Moscatello, A., Saft, M., Cho, J., and Gonzales-Portillo, B. (2021). Pituitary Adenylate Cyclase-Activating Polypeptide: A Potent Therapeutic Agent in Oxidative Stress. Antioxidants, 10.","DOI":"10.3390\/antiox10030354"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1080\/003655201750074492","article-title":"Intestinal adaptation in atrophic rat ileum is accompanied by supersensitivity to vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide and nitric oxide","volume":"36","author":"Ekelund","year":"2001","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S0143-4179(98)90081-6","article-title":"Changes in pituitary adenylate cyclase activating peptide and vasoactive intestinal peptide innervation of rat oxyntic mucosa during ulcer healing","volume":"32","author":"Mei","year":"1998","journal-title":"Neuropeptides"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"151425","DOI":"10.1016\/j.aanat.2019.151425","article-title":"Long-term treatment with naproxen changes the chemical coding of the porcine intramural duodenum neurons","volume":"227","author":"Czajkowska","year":"2020","journal-title":"Ann. Anat."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0167-0115(02)00194-5","article-title":"PAC1 and PACAP expression, signaling, and effect on the growth of HCT8, human colonic tumor cells","volume":"109","author":"Le","year":"2002","journal-title":"Regul. Pept."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.peptides.2015.01.009","article-title":"A structure-function study of PACAP using conformationally restricted analogs: Identification of PAC1 receptor-selective PACAP agonists","volume":"66","author":"Mantey","year":"2015","journal-title":"Peptides"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.peptides.2008.01.022","article-title":"Novel stable PACAP analogs with potent activity towards the PAC1 receptor","volume":"29","author":"Bourgault","year":"2008","journal-title":"Peptides"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1111\/j.1399-3011.1992.tb00324.x","article-title":"Pituitary adenylate cyclase-activating polypeptide (PACAP) with 27 residues. Conformation determined by 1:H NMR and CD spectroscopies and distance geometry in 25% methanol solution","volume":"40","author":"Inooka","year":"1992","journal-title":"Int J. Pept. Protein Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"5832","DOI":"10.1021\/bi00073a016","article-title":"Solution structure of pituitary adenylate cyclase-activating polypeptide by nuclear magnetic resonance spectroscopy","volume":"32","author":"Wray","year":"1993","journal-title":"Biochemistry"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8682\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:44:59Z","timestamp":1760165099000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,12]]},"references-count":113,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijms22168682"],"URL":"https:\/\/doi.org\/10.3390\/ijms22168682","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,12]]}}}