SOMATOSTATIN IS RELEASED IN RESPONSE TO CHOLECYSTOKININ BY ACTIVATIONOF TYPE-A CCK RECEPTORS

Cholecystokinin is a principal mediator of intestinal fat-induced inhi bition of gastric acid secretion, indicating that it is an important p hysiological enterogastrone. Cholecystokinin has been shown to inhibit acid secretion by activation of type A CCK receptors and through a me chanism involving somatostatin. In the present study, we investigated the possibility that these two mechanisms are directly related such th at activation of type A CCK receptors by CCK causes the release of som atostatin. We tested this hypothesis in vivo in a study of CCK-stimula ted release of somatostatin in dogs and in vitro in a study of CCK-sti mulated release of somatostatin from an enriched culture of canine fun dic D cells. In dogs, IV infusion of CCK (50 pmol/kg/h, IV) significan tly increased circulating somatostatin concentrations above basal. Fur ther, systemic administration of somatostatin MAb F(ab)1 fragments of a somatostatin monoclonal antibody prevented most of CCK-induced inhib ition of meal-stimulated acid secretion. In canine fundic D cells in c ulture, CCK-stimulated somatostatin release was blocked in a dose-depe ndent fashion by application of a type A CCK receptor antagonist. This study indicates that CCK activates type A CCK receptors to release so matostatin from canine fundic mucosal D cells, and accounts for somato statin-dependent CCK-induced inhibition of acid secretion.