THE EFFECT OF CCKB/GASTRIN ANTAGONISTS ON STIMULATED GASTRIC-ACID SECRETION IN THE ANESTHETIZED RAT

1 The urethane-anaesthetized, vagotomised rat preparation was used to investigate the effects of the histamine H-2-antagonist ranitidine, the proton pump inhibitor omeprazole and the CCK(B)/gastrin antagonists CI-988, PD 136450 and L-365,260 on pentagastrin-, histamine- and bethanechol-induced gastric acid secretion. 2 The novel CCK(B)/gastrin antagonists CI-988 and PD 136450, and L-365,260 dose-dependently inhibited pentagastrin-induced secretion. The ED50 value for PD 136450 was 0.05-mu-mol kg-1, the same following intravenous or subcutaneous administration. 3 CI-988 and PD 136450 administered subcutaneously at dose levels highly effective for antagonism of pentagastrin responses had no effect on basal acid secretion. 4 Ranitidine inhibited pentagastrin-, bethanechol-, and histamine-induced acid secretion, whereas the CCK(B)/gastrin antagonists inhibited only the secretory response to pentagastrin. 5 The selective CCK(A) antagonist, devazepide, was inactive at up to 300-mu-mol kg-1 i.p. against the three stimulants of acid secretion. 6 CI-988 and PD 136450 will be useful research tools with which to investigate the role of CCK(B)/gastrin receptors in gastric acid secretion and the trophic activities of gastrin and cholecystokinin (CCK) on the gastrointestinal tract.