Effect of cholecystokinin receptor antagonists, MK-329 and L-365,260, on cholecystokinin-induced acid secretion and histidine decarboxylase activity in the rat.
To elucidate the regulatory mechanism of acid secretion by cholecystokinin (CCK) in vivo, we compared the effects of CCK and gastrin on acid secretion and histidine decarboxylase (HDC) activity. We also examined the effects of MK-329, a specific antagonist for pancreatic-type CCK receptor, and L-365,260, a specific antagonist for gastrin-type CCK receptor, on the action of CCK. Graded doses of CCK or gastrin were intravenously infused into conscious rats with gastric fistula. Gastrin-17 I infusion up to 10 nmol/kg/h resulted in dose-related increases in acid secretion. CCK-8 infusion also caused an increase in acid secretion. However, it reached a peak with 0.3 nmol/kg/h CCK-8 and attenuated with higher concentrations of CCK-8. This attenuating effect of a higher dose of CCK was reversed by MK-329, but not by L-365,260. Both CCK and gastrin were potent in increasing fundic HDC activity, and the effect of CCK on HDC activity was significantly inhibited by L-365,260, but not by MK-329. Taken together, the present study suggests that CCK and gastrin stimulate histamine formation via a gastrin-type CCK receptor, and the attenuating action of CCK with higher concentrations on acid secretion in vivo is mediated by a pancreatic-type CCK receptor.
Kawabata
S
S
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Kanayama
S
S
Shinomura
Y
Y
Miyazaki
Y
Y
Imamura
I
I
Moriwaki
K
K
Wada
H
H
Tarui
S
S
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D020109:Devazepide; D005744:Gastric Acid / Q000378:metabolism*; D005748:Gastric Fundus / Q000201:enzymology; D005755:Gastrins / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000378:metabolism*; D007262:Infusions, Intravenous; D008297:Male; D010671:Phenylurea Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D001570:Benzodiazepinones; D005755:Gastrins; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002766:Cholecystokinin; D006640:Histidine Decarboxylase; D020109:Devazepide