Prostaglandin E-type receptor subtypes and gastroduodenal bicarbonate secretion in rats

We investigated the relationship between prostaglandin E‐type receptor (EP receptor) subtypes and gastroduodenal HCO3‐ secretion in rats. Under urethane anaesthesia, a stomach mounted in an ex vivo chamber or a proximal duodenal loop was perfused with saline and the HCO3‐ secretion was measured at pH 7.0 using a pH‐stat method and by adding 10 mmol/L HCl. Prostaglandin E2 (PGE2, i.V.) increased HCO3‐ secretion in both the stomach and duodenum; this action was verapamil sensitive and only in the duodenum was potentiated by isobutylmethyl xanthine (IBMX). Duodenal HCO3‐ secretion was also stimulated by both sulprostone (EP1/EP3 agonist), enprostil (EP1/EP3 agonist), misoprostol (EP2/EP3 agonist), 11‐deoxy PGE1 (EP3/EP4 agonist) and ONO‐NT‐012 (EP3 agonist), but was not affected by either butaprost (EP2 agonist) or 17‐phenyl‐ω‐trinor‐PGE2 (EP1 agonist). In contrast, gastric HCO3‐ secretion was stimulated by sulprostone, enprostil and 17‐phenyl‐ω‐trinor‐PGE2, but not by misoprostol, butaprost, 11‐deoxy PGE1 or ONO‐NT‐012. The EP1 antagonist SC‐51089 inhibited the HCO3‐ stimulatory action of sulprostone in the stomach but not in the duodenum. Isobutylmethyl xanthine potentiated the HCO3‐ response to sulprostone in the duodenum, while verapamil reduced the response in both the stomach and duodenum. These results suggest that PGE2 stimulates HCO3‐ secretion via different EP receptor subtypes in the stomach and duodenum: in the former the EP1 receptors linked to Ca2+ and in the latter, the EP3 receptors coupled with both cAMP and Ca2+.