Effect of cholecystokinin-B/gastrin receptor blockade on gastric acid secretion in conscious rats

Gastrin, histamine and acetylcholine are physiological stimuli of gastric acid secretion. The cholecystokinin-B/gastrin receptor antagonists YM022 and RP73870 were used to study the effect of gastrin receptor blockade on acid secretion. Gastrin, histamine, insulin or bethanechol were administered to conscious gastric fistula rats with or without the concomitant intravenous infusion of YM022 or RP73870. Other rats were subjected to pylorus ligation, YM022 and RP73870 inhibited the gastrin-induced acid secretion in a dose- and time- dependent manner; maximal inhibition was observed at a dose of 0.3 mu mol . kg(-1). hr(-1) for both YM022 and RP73870, the ID50 values being 0.02 mu mol . kg(-1). hr(-1) and 0.05 mu mol . kg(-1). hr(-1) for YM022 and RP73870, respectively. At a dose of 0.3 mu mol . kg(-1). hr(-1) YM022 and RP73870 failed to inhibit basal and histamine-, bethanechol-, and insulin-liked secretion. They also failed to affect the secretion evoked by infusion of a cocktail of maximally effective doses of gastrin-17, histamine and bethanechol. YM022 and RP73870, finally, were without effect on the acid response to pylorus ligation. We suggest that endogenous gastrin in the conscious rat does not contribute to the basal acid secretion and does not participate in the acid response to histamine or to vagus stimulation.