Effects on digestive secretions.

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.