Document Detail

Identity and regulation of stored and secreted progastrin-derived peptides in sheep.
MedLine Citation:
PMID:  15308616     Owner:  NLM     Status:  MEDLINE    
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.
Adrienne C Paterson; Sharon M Lockhart; Josephine Baker; Greg Neumann; Graham S Baldwin; Arthur Shulkes
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-08-12
Journal Detail:
Title:  Endocrinology     Volume:  145     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-10-18     Completed Date:  2004-11-30     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5129-40     Citation Subset:  AIM; IM    
Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Victoria 3084, Australia.
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MeSH Terms
Anti-Ulcer Agents / pharmacology
Gastrins / isolation & purification,  metabolism*,  secretion
Mass Spectrometry
Omeprazole / pharmacology
Peptide Fragments / isolation & purification,  metabolism*,  secretion
Protein Precursors / isolation & purification,  metabolism*,  secretion
Pyloric Antrum / metabolism*,  secretion
Somatostatin / pharmacology
Grant Support
Reg. No./Substance:
0/Anti-Ulcer Agents; 0/Gastrins; 0/Peptide Fragments; 0/Protein Precursors; 51110-01-1/Somatostatin; 53988-98-0/big gastrin; 73590-58-6/Omeprazole

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