Effect of omeprazole on gastric acid secretion by the rat isolated stomach

The inhibitory effect of omeprazole has been investigated on the isolated gastric fundus from immature rats. Omeprazole (10(-7)-10(-5) M) inhibited basal acid secretion, conversely from H2-receptor antagonists, antimuscarinic compounds and calcium antagonists; the effect was mimicked only by KSCN (3 X 10(-4)-3 X 10(-2) M). Omeprazole (10(-6)-10(-5) M) caused an insurmountable antagonism of the hypersecretion induced by histamine and bethanechol, whereas it competitively antagonized the secretory response to isoprenaline and dibutyryl cAMP. Experiments carried out in low calcium media showed that calcium ions did not significantly affect the inhibitory potency of omeprazole when tested on basal acid secretion, whereas low calcium solutions enhanced the action of omeprazole against histamine-induced hypersecretion. The above data confirmed the potent antisecretory activity of omeprazole in different experimental conditions in which the common antisecretagogues are without effect and pointed out the novel site of action in the control of gastric acid secretion at intracellular level.