Determination of Histamine Release in Isolated Gastric Mucosal Cells Gastric mucosal cells were isolated from male Wistar rats

secretion in vivo and in vitro. The inhibitory effect of endogenous NO on stimulated acid secretion has also been demonstrated in rats. Thus, NO is generally thought to inhibit the stimulation of gastric acid secretion. On the contrary, we have demonstrated that NO has a stimulatory effect on gastric acid secretion: Sodium nitroprusside, a NO donor, increases acid secretion in isolated mouse stomach preparations. Additionally, N-nitro-L-arginine, a NO synthase inhibitor, reduces gastric acid secretion induced by cholinergic agents and pentagastrin, suggesting the stimulation of acid secretion by endogenous NO. In the gut, the cells that synthesize and release histamine are mucosal mast cells and enterochromaffin-like (ECL) cells. ECL cells are considered to be the origin of endogenous histamine, which is related to peripheral regulation of gastric acid secretion in rodents. In our previous study, acid secretion induced by sodium nitroprusside and dibutyryl cyclic GMP, a cell-permeable analogue of cyclic GMP, was abolished by the histamine H2 receptor antagonist famotidine in isolated mouse stomach. In addition, N-nitro-L-arginine inhibits bethanecholand pentagastrin-induced histamine release in isolated rat gastric mucosal cell preparations. These findings suggest that NO augments histamine release from the histamine-containing cells, resulting in the increased acid secretion. It is suggested that NO–cyclic GMP system in the histamine-containing cells are involved in enhancement of acid secretion, but whether NO donors induce an increase in histamine release has not yet been demonstrated. In the present study, we investigated the effects of NO donors on histamine release in isolated rat gastric mucosal cells.