Stimulatory effect of dibutyryl cyclic GMP on acid secretion in mouse isolated stomach and on histamine release in gastric mucosal cells

We previously reported that endogenous nitric oxide (NO) is involved in the peripheral control of gastric acid secretion induced by some secretagogues , and that endogenous NO is involved in the acid secretion process via hist amine release from histamine-containing cells. However, the stimulus-secret ion coupling in the cells remains to be clarified. In the present study, we investigated the effect of dibutyryl cyclic GMP on gastric acid secretion in mouse isolated stomach and on histamine release in gastric mucosal cells , in comparison with those of dibutyryl cyclic AMP. Dibutyryl cyclic GMP (3 00 mu M) produced a slight but significant increase of gastric acid secreti on, which was completely inhibited by the histamine-H2 receptor antagonist famotidine. In contrast, dibutyryl cyclic GMP (1 mM) markedly inhibited his tamine-induced acid secretion. Dibutyryl cyclic AMP (100 mu M) produced a s ustained increase of gastric acid secretion. The pretreatment with famotidi ne partially inhibited dibutyryl cyclic AMP-induced gastric acid secretion. Dibutyryl cyclic GMP and dibutyryl cyclic AMP significantly increased the histamine release from gastric mucosal cells. These results suggest that bo th intraceLluIar cyclic GMP and cyclic AMP act as second messengers for his tamine release in the histamine-containing cells, probably ECL cells. On th e other hand, in gastric parietal cells, cyclic AMP has a stimulatory effec t on gastric acid secretion, whereas cyclic GMP has an inhibitory effect. ( C) 2000 Elsevier Science Ltd. Published by editions scientifiques et medica les Elsevier SAS.