IMPORTANCE OF GASTRIN-RELEASING PEPTIDE ON ACID-INDUCED SECRETIN RELEASE AND PANCREATICOBILIARY AND DUODENAL BICARBONATE SECRETION

Background: Exogenous gastrin-releasing peptide (GRP) stimulates the r elease of secretin from the small intestine and pancreaticobiliary bic arbonate secretion in pigs. As acid is the principal stimulant of secr etin release, the purpose of this study was to examine the importance of GRP in acid-induced secretin release and to determine whether GRP c ontributes to the regulatory function of acid-induced pancreaticobilia ry bicarbonate secretion in anaesthetized pigs. Methods and Results: I ntravenous infusion of GRP (500 pmol/kg . h) increased significantly p ortal vein plasma concentrations of secretin from 1.3 to 5.4 pmol/l an d 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 mm ol/h, whereas duodenal mucosal bicarbonate secretion remained unchange d. Intravenous infusion of the GRP antagonist BIM-26226 completely abo lished the GRP-induced secretin release and pancreatic and hepatic bic arbonate secretion. Furthermore, repeated infusions of GRP did not cau se desensitization, and BIM-26226 therefore proved to be an effective GRP antagonist. Duodenal perfusion with acid (pH 1.5, 3.8 mmol/h) sign ificantly 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 p ancreaticobiliary and duodenal bicarbonate secretion. Conclusions: Thu s, we conclude that GRP likely plays an insignificant role in a possib le peptidergic regulation of acid-induced intestinal secretin release and that GRP has no regulatory function in acid-induced pancreaticobil iary bicarbonate secretion. Furthermore, GRP has no effect on duodenal bicarbonate secretion.