The effect of gastrin-releasing peptide on porcine pancreaticobiliary bicarbonate secretion is mediated by secretin.

The effect of gastrin-releasing peptide (GRP) (250, 500, 1000 pmol/kg.h) on the pancreaticobiliary bicarbonate secretion, the pancreatic protein secretion, and the plasma concentrations of secretin and cholecystokinin (CCK) was studied in the anaesthetized pig. Infusion of GRP (1000 pmol/kg.h) increased the portal plasma concentrations of secretin from 0.9 to 13.6 pmol/l and CCK from 1.2 to 38.4 pmol/l, the pancreatic bicarbonate secretion from 0.01 to 5.6 mmol/h, the hepatic bicarbonate secretion from 0.5 to 4.1 mmol/h, and the pancreatic protein secretion from 3 to 680 mg/h. Blocking of CCK-A receptors by MK-329 did not significantly change the effect of GRP, whereas prevention of secretin release by removal of the small intestine caused a 13-fold reduction in the GRP-induced pancreatic bicarbonate secretion and completely abolished the effect on hepatic bicarbonate secretion but did not change the effect on pancreatic protein secretion. We conclude that the effect of GRP on pancreaticobiliary bicarbonate secretion is not mediated through the release of CCK but more likely through the release of secretin and that the effect on pancreatic protein secretion is possibly a direct effect of GRP.