Roles of prostaglandin E-receptor subtypes in gastric and duodenal bicarbonate secretion in rats

Background & Aims: Receptors activated by prostaglandin (PG) E-2, are pharmacologically subdivided into four subtypes (EP1-EP4). The EP-receptor subtype(s) involved in stimulation of gastroduodenal HCO3- secretion in rats were investigated. Methods: Under urethane anesthesia, a stomach mounted in an ex vivo chamber or a proximal duodenal loop was perfused with saline, and HCO3- secretion was measured using a pH-stat method. Results: Intravenous PGE(2) increased HCO3- secretion by the gastroduodenal mucosa; this action was verapamil sensitive and, only in the duodenum, potentiated by isobutylmethyl xanthine (IBMX). Duodenal HCO3- secretion was stimulated by enprostil, sulprostone (EP1/EP3, agonist), misoprostol (EP2/EP3 agonist), and ONO-NT012 (EP3 agonist) but was not affected by butaprost (EP2 agonist) or 17-phenyl-PGE(2), (EP1 agonist). Gastric HCO3- secretion was stimulated by sulprostone, enprostil, and 17-phenyl-PGE, but not by misoprostol, butaprost, or ONO-NT012. SC-51089 (EP1 antagonist) inhibited the HCO3- -stimulatory action of sulprostone only in the stomach. IBMX potentiated the HCO3- response to sulprostone in the duodenum, whereas verapamil reduced the response in both the stomach and duodenum. Conclusions: PGE stimulates HCO3- secretion via different EP-receptor subtypes in the stomach and duodenum: in the stomach, EP1 receptors are linked to Ca2+; in the duodenum, EP3 receptors are coupled with both adenosine 3', 5'-cyclic monophosphate and Ca2+.