Cholecystokinin inhibits gastric acid secretion through type "A" cholecystokinin receptors and somatostatin in rats.
The purpose of this study was to determine whether selective antagonism of type "A" cholecystokinin (CCK) receptors blocks inhibition of gastric acid secretion produced by CCK and whether this inhibition is mediated through either a somatostatin-dependent pathway or a vago-vagal reflex. Intravenous infusion of CCK (0.04-10 nmol.kg-1.h-1) dose dependently inhibited pentagastrin-stimulated gastric acid secretion in urethan-anesthetized rats, with a 50% inhibitory dose of 0.9 nmol.kg-1.h-1 and a maximum inhibition of approximately 50%. Blockade of type A CCK receptors using the selective type A receptor antagonist MK-329 completely reversed the inhibitory effect produced by a maximal dose (4 nmol.kg-1.h-1) of CCK. Immunoneutralization of endogenous somatostatin by administration of somatostatin monoclonal antibody abolished the inhibition produced by CCK. Concentrations of somatostatin in portal venous plasma were significantly increased after CCK administration; the increase in somatostatin was blocked by pretreatment with MK-329. In contrast, CCK-induced inhibition of gastric acid secretion was unaltered after perivagal capsaicin treatment. These results indicate that CCK inhibits gastric acid secretion in rats by activation of type A CCK receptors and through release of endogenous somatostatin.
Research Service, Department of Veterans Affairs, Los Angeles, California.
K C
KC
Lloyd
H E
HE
Raybould
J H
JH
Walsh
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001570:Benzodiazepinones / Q000494:pharmacology; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D020109:Devazepide; D005744:Gastric Acid / Q000378:metabolism*; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D013004:Somatostatin / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014630:Vagus Nerve
D000911:Antibodies, Monoclonal; D001570:Benzodiazepinones; D011949:Receptors, Cholecystokinin; D013004:Somatostatin; D002766:Cholecystokinin; D010418:Pentagastrin; D020109:Devazepide; D002211:Capsaicin