ROLE OF GASTRIN AND CHOLECYSTOKININ RECEPTORS IN REGULATION OF PEPTONE-STIMULATED GASTRIC-ACID SECRETION IN CONSCIOUS RATS

With the availability of selective gastrin/CCK(B) (L365,260) and CCK, (L364,718) receptor antagonists the present study was designed to inve stigate the role of gastrin and cholecystokinin (CCK) receptors in mea l-stimulated gastric acid secretion. Gastric acid output was measured by continuous intragastric titration in conscious rats. Vehicle (dimet hylsulfoxide/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. Intr agastric peptone (4%, w/v) increased acid secretion 40-65% of the resp onse to a maximal dose (2.5 nmol/kg per h) of gastrin-17. L365,260 com pletely abolished gastrin-17 stimulated acid secretion and partially i nhibited peptone-induced acid secretion. Blockade of CCK(A) receptors by L364,718 did not affect peptone-stimulated acid output. This study demonstrates that gastrin/CCK(B) receptors are important in regulating basal acid secretion in the conscious rat while CCK(A) receptors do n ot appear to influence basal or peptone-stimulated gastric acid secret ion. Blockade of gastrin/CCK(B) receptors partially inhibits intragast ric meal-stimulated acid secretion indicating that the gastrin/CCK(B) receptor has a physiological role as mediator of food-stimulated acid secretory response in conscious rats.