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-rece ptor subtype(s) involved in stimulation of gastroduodenal HCO3- secret ion in rats were investigated. Methods: Under urethane anesthesia, a s tomach mounted in an ex vivo chamber or a proximal duodenal loop was p erfused with saline, and HCO3- secretion was measured using a pH-stat method. Results: Intravenous PGE(2) increased HCO3- secretion by the g astroduodenal 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, ag onist), 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, enpr ostil, and 17-phenyl-PGE, but not by misoprostol, butaprost, or ONO-NT 012. SC-51089 (EP1 antagonist) inhibited the HCO3- -stimulatory action of sulprostone only in the stomach. IBMX potentiated the HCO3- respon se to sulprostone in the duodenum, whereas verapamil reduced the respo nse in both the stomach and duodenum. Conclusions: PGE stimulates HCO3 - secretion via different EP-receptor subtypes in the stomach and duod enum: in the stomach, EP1 receptors are linked to Ca2+; in the duodenu m, EP3 receptors are coupled with both adenosine 3', 5'-cyclic monopho sphate and Ca2+.