Effects of proglumide on cholecystokinin-8-induced exocrine and endocrine pancreatic responses in conscious sheep.

The effects of cholecystokinin (CCK)-8, either alone or together with the CCK antagonist, proglumide on both exocrine and endocrine pancreatic responses were examined in conscious sheep. Intravenous infusions of CCK-8 (120 pmol/kg/min for 40 min) with vehicle (0 mumol/kg/min proglumide) significantly increased both amylase output in pancreatic juice and plasma insulin concentrations (P < 0.05). Concomitant infusions of proglumide (5-40 mumol/kg/min for 50 min) inhibited both amylase and insulin secretory responses induced by CCK-8 infusion. The antagonistic effects of proglumide occurred in a dose-dependent manner, and proglumide infusion at dose of 20 mumol/kg/min or above simultaneously inhibited CCK-8-induced amylase and insulin responses. In conclusion, although the type of receptor involved is not characterized at present, exogenously infused CCK-8 acts on B cells via a CCK-receptor-mediated mechanism and induces insulin secretion in sheep.