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⁺ .