Effect of glycyrrhetinic acid on the cyclic nucleotide system of the rat stomach

Abstract Glycyrrhetinic acid (carbenoxolone) inhibited cyclic nucleotide phosphodiesterase (PDE) activity in a number of tissues from rat, guinea pig and dog. In the fundic mucosa, it was more active when cyclic AMP rather than cyclic GMP was used as substrate in the PDE assays. Glycyrrhetinic acid also raised the intracellular levels of cyclic AMP in rat pyloric and fundic mucosae in vivo with little effect on cyclic GMP levels. This effect, at least in the rat, was apparently mediated via PDE-inhibition, since the drug did not affect adenylyl cyclase activity from either mucosa. Studies with theophylline and papaverine, in addition to glycyrrhetinic acid, suggested that the effects of PDE inhibitors on gastric acid secretion could be related to their relative activities on cyclic AMP-PDE's or cyclic GMP-PDE's, owing to the possibly opposite effects mediated by the two cyclic nucleotides on acid secretion by the stomach.