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 pancreat ic responses were examined in conscious sheep. Intravenous infusions o f CCK-8 (120 pmol/kg/min for 40 min) with vehicle (0 mu mol/kg/min pro glumide) significantly increased both amylase output in pancreatic jui ce and plasma insulin concentrations (P < 0.05). Concomitant infusions of proglumide (5-40 mu mol/kg/min for 50 min) inhibited both amylase and insulin secretory responses induced by CCK-8 infusion. The antagon istic effects of proglumide occurred in a dose-dependent manner, and p roglumide infusion at dose of 20 mu mol/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 presen t, exogenously infused CCK-8 acts on B cells via a CCK-receptor-mediat ed mechanism and induces insulin secretion in sheep. (C) 1997 Elsevier Science Inc.