Antisecretory and antigastrin effects of rioprostil in gastric fistula dogs.

Abstract

This investigation examined the effect of rioprostil, a primary alcohol prostaglandin E1 analog, on betazole-stimulated gastric acid secretion and on basal and food-stimulated (postprandial) serum gastrin levels in gastric fistula dogs. Rioprostil inhibited betazole-stimulated gastric acid secretion with an ED50 of 16 (10-24) micrograms/kg, intragastrically. A near-maximal gastric antisecretory dose (100 micrograms/kg, intragastrically) had no effect on basal serum gastrin levels but significantly attenuated the rapid rise in serum gastrin which follows feeding, a result different from that reported for other prostaglandin E1 analogs. A nonantisecretory dose of rioprostil (1.0 micrograms/kg, intragastrically) also attenuated the rise in postprandial serum gastrin. An antigastrin effect using a nonantisecretory dose of an antiulcer agent has not been reported previously and may indicate that rioprostil has a direct inhibitory effect on secretion of gastrin. The ability of rioprostil to inhibit gastric acid secretion and decrease postprandial peak serum gastrin levels, coupled with previously established cytoprotective efficacy, makes it an attractive clinical candidate for the treatment and prevention of peptic ulcer disease.