Document Detail


Effects on digestive secretions.
MedLine Citation:
PMID:  16492544     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Rat amylin subcutaneously injected into rats dose-dependently inhibits pentagastrin-stimulated gastric acid secretion and protects the stomach from ethanol-induced gastritis. The ED50s for these actions (0.050 and 0.036 microg, respectively) are the lowest for any dose-dependent effect of amylin thus far described, and their similar potencies are consistent with a mechanistic (causal) association. At higher amylin doses, inhibition of gastric acid secretion was almost complete (93.4%). Gastric injury (measured by a subjective analog scale) was inhibited by up to 67%. The observation that effective doses of amylin result in plasma concentrations of 7-10 pM (i.e., within the reported range; Pieber et al., 1994) supports the interpretation that inhibition of gastric acid secretion and maintenance of gastric mucosal integrity are physiological actions of endogenous amylin. The pharmacology of these responses fits with one mediated via amylin-like receptors. Rat amylin inhibited CCK-stimulated secretion of pancreatic enzymes,amylase, and lipase by up to approximately 60% without having significant effect in the absence of CCK. ED50s for the effect were in the 0.1-0.2 microg range, calculated to produce plasma amylin excursions within the physiological range. Effects of informative ligands are consistent with the concept of amylin receptor mediation. Amylin was effective in ameliorating the severity of pancreatitis in a rodent model. The amylin analog pramlintide inhibited gallbladder emptying in mice as measured by total weight of acutely excised gallbladders. Amylin inhibition of gastric acid secretion, pancreatic enzyme secretion, and bile secretion likely represents part of an orchestrated control of nutrient appearance. Modulation of digestive function fits with a general role of amylin in regulating nutrient uptake. Rate of ingestion, rate of release from the stomach, and rate of digestion of various food groups appear to be under coordinate control.
Authors:
Andrew Young
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Advances in pharmacology (San Diego, Calif.)     Volume:  52     ISSN:  1054-3589     ISO Abbreviation:  Adv. Pharmacol.     Publication Date:  2005  
Date Detail:
Created Date:  2006-02-22     Completed Date:  2006-03-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9015397     Medline TA:  Adv Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  123-50     Citation Subset:  IM    
Affiliation:
Amylin Pharmaceuticals, Inc., San Diego, California, USA.
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MeSH Terms
Descriptor/Qualifier:
Amyloid / pharmacology*,  physiology
Animals
Anti-Ulcer Agents / pharmacology
Digestive System / drug effects*,  metabolism
Dose-Response Relationship, Drug
Gastric Acid / secretion
Rats
Chemical
Reg. No./Substance:
0/Amyloid; 0/Anti-Ulcer Agents; 106602-62-4/amylin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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