AUGMENTATION OF THE INHIBITORY EFFECT OF FK480, A CCK-A RECEPTOR ANTAGONIST, ON PANCREATIC EXOCRINE SECRETION BY ACHLORHYDRIA

The effect of intraluminal acid and cholecystokinin (CCK) receptor blo ckade on the pancreatic secretory response was examined in rats. Block ade of gastric acid secretion by YM022 (CCK-B receptor antagonist) or famotidine (histamine-2 receptor antagonist) resulted in a significant suppression of casein-stimulated pancreatic exocrine secretion as det ermined by juice volume and amylase secretion. Ligation of the gastric pylorus, which leads to complete prevention of gastric acid from ente ring the duodenum, also suppressed pancreatic exocrine secretion. FK48 0 (CCK-A receptor antagonist) inhibited pancreatic exocrine secretion dose dependently at doses of 0.01-1.0 mg/kg, When submaximal doses of FK480 and YM022 were treated concomitantly, pancreatic exocrine secret ion was inhibited more profoundly than when treated solely. Hydrochlor ic acid (HCI; 0.05 N), injected into the duodenum, stimulated pancreat ic exocrine secretion to a level comparable to that exhibited by intra duodenal casein. This effect of HCI was inhibited by FK480 (1.0 mg/kg) but not by YM022 (1.0 mg/kg). These findings suggest that inhibition of gastric acid secretion leads to the suppression of pancreatic exocr ine secretion through mechanisms mediated by CCK-A receptors.