{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T09:48:10Z","timestamp":1694166490951},"reference-count":52,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Amidated and nonamidated progastrin-derived peptides have distinct biological activities that are mediated by a range of receptor subtypes. The objective was to determine the nature of the stored and secreted progastrin-derived peptides and to investigate whether progastrin release is regulated by gastric acidity. Using an antiserum directed to the C terminus of progastrin for identification and to monitor purification, C-terminal flanking peptides (CTFP) of progastrin (prog76\u201383, prog77\u201383, and prog78\u201383 in approximately equivalent amounts) were isolated and identified from extracts of sheep antrum using ion exchange, HPLC, and mass spectrometry. Only trace amounts of full-length progastrin were present. Progastrin CTFP was the predominant progastrin-derived peptide in the antrum [progastrin CTFP\/gastrin amide (Gamide) = 3]. Similarly, progastrin CTFP was the major circulating form in the antral (CTFP, 710 \u00b1 62 pmol\/liter; Gamide, 211 \u00b1 35 pmol\/liter) and jugular (CTFP, 308 \u00b1 16 pmol\/liter; gastrin amide, 32 \u00b1 3 pmol\/liter) veins. Alteration of gastric acidity in sheep by iv infusion of a H\/K-adenosine triphosphatase inhibitor or somatostatin or by intragastric infusion of HCl demonstrated that the CTFP concentrations changed, although to a lesser extent than the changes in circulating gastrin amide. We conclude that the CTFP of progastrin is the major stored and circulating species of the gastrin gene, and that it is secreted in a regulated fashion rather than constitutively. Because full-length progastrin is bioactive, but is only a minor antral and secreted form, determination of the biological activity of the C-terminal flanking peptides will be important for a complete understanding of gastrin endocrinology.<\/jats:p>","DOI":"10.1210\/en.2004-0912","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T00:15:20Z","timestamp":1092356120000},"page":"5129-5140","source":"Crossref","is-referenced-by-count":8,"title":["Identity and Regulation of Stored and Secreted Progastrin-Derived Peptides in Sheep"],"prefix":"10.1210","volume":"145","author":[{"given":"Adrienne C.","family":"Paterson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon M.","family":"Lockhart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josephine","family":"Baker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham S.","family":"Baldwin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur","family":"Shulkes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071614211478500_R1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1152\/physrev.1995.75.1.155","article-title":"Gastric acid secretion.","volume":"75","author":"Hersey","year":"1995","journal-title":"Physiol Rev"},{"key":"2020071614211478500_R2","first-page":"75","author":"Walsh","year":"1994"},{"key":"2020071614211478500_R3","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1152\/physrev.1996.76.3.767","article-title":"Gastric endocrine cells: gene expression, processing, and targeting of active products.","volume":"76","author":"Dockray","year":"1996","journal-title":"Physiol Rev"},{"key":"2020071614211478500_R4","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1152\/physrev.1998.78.4.1087","article-title":"The new biology of gastrointestinal hormones.","volume":"78","author":"Rehfeld","year":"1998","journal-title":"Physiol Rev"},{"key":"2020071614211478500_R5","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1136\/gut.42.4.581","article-title":"Gastrin, gastrin receptors and colorectal carcinoma.","volume":"42","author":"Baldwin","year":"1998","journal-title":"Gut"},{"key":"2020071614211478500_R6","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1146\/annurev.physiol.63.1.119","article-title":"The gastrins: their production and biological activities.","volume":"63","author":"Dockray","year":"2001","journal-title":"Annu Rev Physiol"},{"key":"2020071614211478500_R7","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/S0016-5085(97)70172-0","article-title":"Regulation of growth of human gastric cancer by gastrin and glycine-extended progastrin.","volume":"113","author":"Iwase","year":"1997","journal-title":"Gastroenterology"},{"key":"2020071614211478500_R8","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0167-0115(00)00176-2","article-title":"Gastrin as a growth factor in the gastrointestinal tract.","volume":"93","author":"Koh","year":"2000","journal-title":"Regul Pept"},{"key":"2020071614211478500_R9","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1053\/gast.2000.16480","article-title":"Glycine-extended gastrin synergizes with gastrin 17 to stimulate acid secretion in gastrin-deficient mice.","volume":"119","author":"Chen","year":"2000","journal-title":"Gastroenterology"},{"key":"2020071614211478500_R10","first-page":"G810","article-title":"Inhibition of the a amidation of gastrin; effects on gastric acid secretion","volume":"258","author":"Dickinson","year":"1990","journal-title":"Am J Physiol"},{"key":"2020071614211478500_R11","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1159\/000201308","article-title":"Metabolism and influence of glycine-extended gastrin on gastric acid secretion in man.","volume":"57","author":"Palnaes Hansen","year":"1996","journal-title":"Digestion"},{"key":"2020071614211478500_R12","first-page":"G220","article-title":"Glycine-extended gastrin potentiates gastrin-stimulated gastric acid secretion in rats","volume":"270","author":"Higashide","year":"1996","journal-title":"Am J Physiol"},{"key":"2020071614211478500_R13","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0167-0115(89)90264-4","article-title":"The constitution and properties of phosphorylated and unphosphorylated C-terminal fragments of progastrin from dog and ferret antrum.","volume":"25","author":"Desmond","year":"1989","journal-title":"Regul Pept"},{"key":"2020071614211478500_R14","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0014-2999(98)00846-2","article-title":"Biological activity of carboxy-terminal gastrin analogs.","volume":"364","author":"Sandvik","year":"1999","journal-title":"Eur J Pharmacol"},{"key":"2020071614211478500_R15","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1172\/JCI118993","article-title":"Processing and proliferative effects of human progastrin in transgenic mice.","volume":"98","author":"Wang","year":"1996","journal-title":"J Clin Invest"},{"key":"2020071614211478500_R16","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1172\/JCI4910","article-title":"Overexpression of glycine-extended gastrin in transgenic mice results in increased colonic proliferation.","volume":"103","author":"Koh","year":"1999","journal-title":"J Clin Invest"},{"key":"2020071614211478500_R17","doi-asserted-by":"crossref","first-page":"7791","DOI":"10.1074\/jbc.M009985200","article-title":"Biologically active recombinant human progastrin(6\u201380) contains a tightly bound calcium ion.","volume":"276","author":"Baldwin","year":"2001","journal-title":"J Biol Chem"},{"key":"2020071614211478500_R18","first-page":"G328","article-title":"Progastrin1\u201380 stimulates growth of intestinal epithelial cells in vitro via high-affinity binding sites","volume":"284","author":"Singh","year":"2003","journal-title":"Am J Physiol"},{"key":"2020071614211478500_R19","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0065-230X(08)60403-0","article-title":"The tumor biology of gastrin and cholecystokinin.","volume":"63","author":"Rehfeld","year":"1994","journal-title":"Adv Cancer Res"},{"key":"2020071614211478500_R20","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/0016-5085(95)90572-3","article-title":"Expression, processing, and secretion of gastrin in patients with colorectal carcinoma.","volume":"109","author":"Ciccotosto","year":"1995","journal-title":"Gastroenterology"},{"key":"2020071614211478500_R21","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/0016-5085(93)90279-L","article-title":"Expression but incomplete maturation of progastrin in colorectal carcinomas.","volume":"104","author":"Van Solinge","year":"1993","journal-title":"Gastroenterology"},{"key":"2020071614211478500_R22","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1136\/gut.34.1.90","article-title":"Identification of progastrin derived peptides in colorectal carcinoma extracts.","volume":"34","author":"Nemeth","year":"1993","journal-title":"Gut"},{"key":"2020071614211478500_R23","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1016\/0016-5085(87)90623-8","article-title":"Progastrin and its glycine-extended posttranslational processing intermediates in human gastrointestinal tissues.","volume":"92","author":"Del Valle","year":"1987","journal-title":"Gastroenterology"},{"key":"2020071614211478500_R24","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/0016-5085(89)91624-7","article-title":"Progastrin processing during antral G-cell hypersecretion in humans.","volume":"96","author":"Jensen","year":"1989","journal-title":"Gastroenterology"},{"key":"2020071614211478500_R25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0167-0115(85)90073-4","article-title":"Identification by specific radioimmunoassay of two novel peptides derived from the C-terminus of porcine preprogastrin.","volume":"11","author":"Desmond","year":"1985","journal-title":"Regul Pept"},{"key":"2020071614211478500_R26","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1172\/JCI112315","article-title":"Identification of progastrin in gastrinomas, antrum, and duodenum by a novel radioimmunoassay.","volume":"77","author":"Pauwels","year":"1986","journal-title":"J Clin Invest"},{"key":"2020071614211478500_R27","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1042\/bj2560951","article-title":"The human gastrin precursor. Characterization of phosphorylated forms and fragments.","volume":"256","author":"Varro","year":"1988","journal-title":"Biochem J"},{"key":"2020071614211478500_R28","doi-asserted-by":"crossref","first-page":"21476","DOI":"10.1016\/S0021-9258(18)45762-6","article-title":"Processing of the gastrin precursor. Modulation of phosphorylated, sulfated, and amidated products.","volume":"265","author":"Varro","year":"1990","journal-title":"J Biol Chem"},{"key":"2020071614211478500_R29","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/0016-5085(87)91022-5","article-title":"Effects of bombesin on the release of glycine-extended progastrin (gastrin G) in rat antral tissue culture.","volume":"93","author":"Azuma","year":"1987","journal-title":"Gastroenterology"},{"key":"2020071614211478500_R30","first-page":"G502","author":"Sugano"},{"key":"2020071614211478500_R31","first-page":"G665","article-title":"Corelease of amidated and glycine-extended antral gastrins after a meal","volume":"255","author":"Hilsted","year":"1988","journal-title":"Am J Physiol"},{"key":"2020071614211478500_R32","first-page":"G802","article-title":"Pharmacokinetics and organ specific metabolism of glycine-extended and amidated gastrin in sheep","volume":"263","author":"Ciccotosto","year":"1992","journal-title":"Am J Physiol"},{"key":"2020071614211478500_R33","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/S0016-5085(87)91070-5","article-title":"Biosynthesis of gastrin. Localization of the precursor and peptide products using electron microscopic-immunogold methods.","volume":"92","author":"Rahier","year":"1987","journal-title":"Gastroenterology"},{"key":"2020071614211478500_R34","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/j.1469-7793.1999.0315p.x","article-title":"Topical review. Gastrin and gastric epithelial physiology.","volume":"518","author":"Dockray","year":"1999","journal-title":"J Physiol"},{"key":"2020071614211478500_R35","first-page":"E449","article-title":"Metabolism of recombinant progastrin in sheep","volume":"283","author":"Paterson","year":"2002","journal-title":"Am J Physiol"},{"key":"2020071614211478500_R36","first-page":"G742","article-title":"Regulation of fundic and antral somatostatin secretion by CCK and gastrin","volume":"274","author":"Zavros","year":"1998","journal-title":"Am J Physiol"},{"key":"2020071614211478500_R37","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3109\/10425179709020883","article-title":"Molecular cloning and sequence of the ovine gastrin gene.","volume":"8","author":"Moore","year":"1997","journal-title":"DNA Seq"},{"key":"2020071614211478500_R38","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1210\/endo-129-5-2329","article-title":"Regulation of somatostatin secretion by gastrin- and acid-dependent mechanisms.","volume":"129","author":"Shulkes","year":"1991","journal-title":"Endocrinology"},{"key":"2020071614211478500_R39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0167-0115(92)90080-E","article-title":"Achlorhydria induced changes in gastrin, somatostatin, H+\/K+-ATPase and carbonic anhydrase in the sheep.","volume":"40","author":"Read","year":"1992","journal-title":"Regul Pept"},{"key":"2020071614211478500_R40","first-page":"G904","article-title":"Modulation of posttranslational processing of gastrin precursor in dogs","volume":"258","author":"Varro","year":"1990","journal-title":"Am J Physiol"},{"key":"2020071614211478500_R41","doi-asserted-by":"crossref","first-page":"5488","DOI":"10.1074\/jbc.M310547200","article-title":"Progastrin is directed to the regulated secretory pathway by synergistically acting basic and acidic motifs.","volume":"279","author":"Bundgaard","year":"2004","journal-title":"J Biol Chem"},{"key":"2020071614211478500_R42","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/ijc.1483","article-title":"Short term infusion of glycine-extended gastrin17 stimulates both proliferation and formation of aberrant crypt foci in rat colonic mucosa.","volume":"94","author":"Aly","year":"2001","journal-title":"Int J Cancer"},{"key":"2020071614211478500_R43","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1053\/gast.2000.8527","article-title":"Progastrin expression predisposes mice to colon carcinomas and adenomas in response to a chemical carcinogen.","volume":"119","author":"Singh","year":"2000","journal-title":"Gastroenterology"},{"key":"2020071614211478500_R44","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1073\/pnas.83.9.2832","article-title":"Cholecystokinin-associated COOH-terminal peptides are fully sulfated in pig brain.","volume":"83","author":"Eng","year":"1986","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614211478500_R45","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/0014-5793(86)80849-3","article-title":"Isolation, structure and properties of the C-terminal flanking peptide of preprocholecystokinin from rat brain.","volume":"204","author":"Varro","year":"1986","journal-title":"FEBS Lett"},{"key":"2020071614211478500_R46","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/0014-5793(86)80203-4","article-title":"Is the C-terminal flanking peptide of rat cholecystokinin double sulphated?","volume":"196","author":"Adrian","year":"1986","journal-title":"FEBS Lett"},{"key":"2020071614211478500_R47","doi-asserted-by":"crossref","first-page":"8643","DOI":"10.1016\/S0021-9258(18)47462-5","article-title":"Post-translational processing of the porcine gastrin precursor by phosphorylation of the COOH-terminal fragment.","volume":"262","author":"Dockray","year":"1987","journal-title":"J Biol Chem"},{"key":"2020071614211478500_R48","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0167-4838(88)90064-7","article-title":"A novel gastrin-processing pathway in mammalian antrum.","volume":"954","author":"Power","year":"1988","journal-title":"Biochim Biophys Acta"},{"key":"2020071614211478500_R49","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0167-0115(87)90014-0","article-title":"Identification of gastrin molecular variants in gastrinoma syndrome.","volume":"17","author":"Kothary","year":"1987","journal-title":"Regul Pept"},{"key":"2020071614211478500_R50","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1159\/000241606","article-title":"Effect of somatostatin on basal concentrations of gastrin and pancreatic polypeptide in the fetal sheep.","volume":"42","author":"Shulkes","year":"1982","journal-title":"Biol Neonate"},{"key":"2020071614211478500_R51","doi-asserted-by":"crossref","first-page":"11155","DOI":"10.1074\/jbc.270.19.11155","article-title":"Glycine-extended progastrin processing intermediates induce H+,K+-ATPase \u03b1-subunit gene expression through a novel receptor.","volume":"270","author":"Kaise","year":"1995","journal-title":"J Biol Chem"},{"key":"2020071614211478500_R52","first-page":"942","article-title":"Helicobacter pylori-associated gastric cancer in INS-GAS mice is gender specific.","volume":"63","author":"Fox","year":"2003","journal-title":"Cancer Res"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/145\/11\/5129\/9023826\/endo5129.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/145\/11\/5129\/9023826\/endo5129.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T23:53:45Z","timestamp":1624578825000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/145\/11\/5129\/2500504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,11,1]]},"references-count":52,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2004,11,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2004-0912","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,11,1]]}}}