Role of gastrin and cholecystokinin receptors in regulation of peptone-stimulated gastric acid secretion in conscious rats.
With the availability of selective gastrin/CCKB (L365,260) and CCKA (L364,718) receptor antagonists the present study was designed to investigate the role of gastrin and cholecystokinin (CCK) receptors in meal-stimulated gastric acid secretion. Gastric acid output was measured by continuous intragastric titration in conscious rats. Vehicle (dimethylsulfoxide/saline, 3:1), L365,260 (3 or 9 mg/kg), or L364,718 (1 mg/kg) was given by i.v. bolus injection. Basal acid output was strongly inhibited by both doses of L365,260 while L364,718 had no effect. Intragastric peptone (4%, w/v) increased acid secretion 40-65% of the response to a maximal dose (2.5 nmol/kg per h) of gastrin-17. L365,260 completely abolished gastrin-17 stimulated acid secretion and partially inhibited peptone-induced acid secretion. Blockade of CCKA receptors by L364,718 did not affect peptone-stimulated acid output. This study demonstrates that gastrin/CCKB receptors are important in regulating basal acid secretion in the conscious rat while CCKA receptors do not appear to influence basal or peptone-stimulated gastric acid secretion. Blockade of gastrin/CCKB receptors partially inhibits intragastric meal-stimulated acid secretion indicating that the gastrin/CCKB receptor has a physiological role as mediator of food-stimulated acid secretory response in conscious rats.
Varga
G
G
Department of Physiology, University of Kansas Medical Center, Kansas City.
Campbell
D R
DR
Bussjaeger
L J
LJ
Solomon
T E
TE
D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D004435:Eating; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D010461:Peptones / Q000494:pharmacology*; D010671:Phenylurea Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*
D001570:Benzodiazepinones; D005755:Gastrins; D006728:Hormones; D010461:Peptones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; C013550:gastrin 17; D002766:Cholecystokinin; D020109:Devazepide