Somatostatin is released in response to cholecystokinin by activation of type A CCK receptors.
Cholecystokinin is a principal mediator of intestinal fat-induced inhibition of gastric acid secretion, indicating that it is an important physiological enterogastrone. Cholecystokinin has been shown to inhibit acid secretion by activation of type A CCK receptors and through a mechanism involving somatostatin. In the present study, we investigated the possibility that these two mechanisms are directly related such that activation of type A CCK receptors by CCK causes the release of somatostatin. We tested this hypothesis in vivo in a study of CCK-stimulated release of somatostatin in dogs and in vitro in a study of CCK-stimulated release of somatostatin from an enriched culture of canine fundic D cells. In dogs, IV infusion of CCK (50 pmol/kg/h, IV) significantly increased circulating somatostatin concentrations above basal. Further, systemic administration of somatostatin MAb F(ab)1 fragments of a somatostatin monoclonal antibody prevented most of CCK-induced inhibition of meal-stimulated acid secretion. In canine fundic D cells in culture, CCK-stimulated somatostatin release was blocked in a dose-dependent fashion by application of a type A CCK receptor antagonist. This study indicates that CCK activates type A CCK receptors to release somatostatin from canine fundic mucosal D cells, and accounts for somatostatin-dependent CCK-induced inhibition of acid secretion.
Lloyd
K C
KC
Research Service, Department of Veterans Affairs, Los Angeles, CA.
Maxwell
V
V
Chuang
C N
CN
Wong
H C
HC
Soll
A H
AH
Walsh
J H
JH
D000143:Acids / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020109:Devazepide; D004285:Dogs; D004435:Eating / Q000502:physiology; D005748:Gastric Fundus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D013004:Somatostatin / Q000097:blood / Q000276:immunology / Q000378:metabolism*
D000143:Acids; D000911:Antibodies, Monoclonal; D001570:Benzodiazepinones; D011949:Receptors, Cholecystokinin; D013004:Somatostatin; D002766:Cholecystokinin; D020109:Devazepide