Sulfonylurea effects on acid and pepsinogen secretion in isolated rabbit gastric glands

The influence of different sulfonylureas on the rate of acid and pepsinogen secretion was studied in isolated rabbit gastric glands. Neither tolbutamide (10-500 mu M), chlorpropamide (10-500 mu M), glibenclamide (1-50 mu M) nor glipizide (1-50 mu M) exerted a secretory effect. In contrast, gliquidone caused a marked and dose-dependent stimulation of acid production in gastric glands incubated under basal conditions and potentiated the stimulatory effect of both histamine and carbachol. Gliquidone also increased the rate of pepsinogen release in gastric glands incubated either under basal conditions or in the presence of cholecystokinin-octapeptide or isoproterenol. The secretory effects of gliquidone were associated with a significant increase in the glandular content of cyclic AMP, caused by a competitive inhibition of low-K-m cyclic AMP phosphodiesterase. Our results indicate that, among the assayed sulfonylureas, only gliquidone, in the micromolar range, stimulates acid and pepsinogen secretion through a cyclic AMP-dependent mechanism. (C) 1998 Elsevier Science B.V.