Importance of gastrin-releasing peptide on acid-induced secretin release and pancreaticobiliary and duodenal bicarbonate secretion.

Abstract

Exogenous gastrin-releasing peptide (GRP) stimulates the release of secretin from the small intestine and pancreaticobiliary bicarbonate secretion in pigs. As acid is the principal stimulant of secretin release, the purpose of this study was to examine the importance of GRP in acid-induced secretin release and to determine whether GRP contributes to the regulatory function of acid-induced pancreaticobiliary bicarbonate secretion in anaesthetized pigs. Intravenous infusion of GRP (500 pmol/kg.h) increased significantly portal vein plasma concentrations of secretin from 1.3 to 5.4 pmol/l and GRP from 0.5 to 340 pmol/l, pancreatic bicarbonate secretion from 0.01 to 5.9 mmol/h, and hepatic bicarbonate secretion from 0.3 to 3.3 mmol/h, whereas duodenal mucosal bicarbonate secretion remained unchanged. Intravenous infusion of the GRP antagonist BIM-26226 completely abolished the GRP-induced secretin release and pancreatic and hepatic bicarbonate secretion. Furthermore, repeated infusions of GRP did not cause desensitization, and BIM-26226 therefore proved to be an effective GRP antagonist. Duodenal perfusion with acid (pH 1.5, 3.8 mmol/h) significantly increased portal vein plasma concentrations of secretin from 0.4 to 2.8 pmol/l, pancreatic bicarbonate secretion from 0.005 mmol/h to 0.19 mmol/h, hepatic bicarbonate secretion from 0.63 to 2.17 mmol/h, and duodenal mucosal bicarbonate secretion from 0.1 to 1.20 mmol/h. Of importance, infusion of BIM-26226 did not significantly alter the effect of intraduodenal acidification on plasma secretin release and pancreaticobiliary and duodenal bicarbonate secretion. Thus, we conclude that GRP likely plays an insignificant role in a possible peptidergic regulation of acid-induced intestinal secretin release and that GRP has no regulatory function in acid-induced pancreaticobiliary bicarbonate secretion. Furthermore, GRP has no effect on duodenal bicarbonate secretion.