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Title: Identity and regulation of stored and secreted progastrin-derived peptides in sheep.
Austin Authors: Paterson, Adrienne C;Lockhart, Sharon M;Baker, Josephine;Neumann, Greg;Baldwin, Graham S;Shulkes, Arthur
Affiliation: Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Victoria 3084, Australia
Issue Date: 12-Aug-2004
Publication information: Endocrinology 2004; 145(11): 5129-40
Abstract: 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 (prog(76-83), prog(77-83), and prog(78-83) 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 +/- 62 pmol/liter; Gamide, 211 +/- 35 pmol/liter) and jugular (CTFP, 308 +/- 16 pmol/liter; gastrin amide, 32 +/- 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.
Gov't Doc #: 15308616
DOI: 10.1210/en.2004-0912
Journal: Endocrinology
Type: Journal Article
Subjects: Anesthesia
Anti-Ulcer Agents.pharmacology
Gastrins.isolation & purification.metabolism.secretion
Mass Spectrometry
Peptide Fragments.isolation & purification.metabolism.secretion
Protein Precursors.isolation & purification.metabolism.secretion
Pyloric Antrum.metabolism.secretion
Appears in Collections:Journal articles

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