title: Involvement of prostaglandin E receptor EP3 subtype in duodenal bicarbonate secretion in rats.
abstract: We investigated the involvement of prostaglandin E (PGE) receptor subtype EP3 in the regulatory mechanism of duodenal HCO(3)(-) secretion in rats. A proximal duodenal loop or a chambered stomach was perfused with saline, and HCO(3)(-) secretion was measured using a pH-stat method and by adding 2 mM HCl. Mucosal acidification was achieved through 10 min of exposure to 10 mM HCl in the duodenum or 100 mM HCl in the stomach. Various EP agonists or the EP4 antagonist were given i.v., while the EP1 or EP3 antagonist was given s.c. or i.d., respectively. Sulprostone (EP1/EP3 agonists) stimulated duodenal HCO(3)(-) secretion in a dose-dependent manner, and this response was inhibited by AE5-599 (EP3 antagonist) but not AE3-208 (EP4 antagonist). AE1-329 (EP4 agonist) also increased duodenal HCO(3)(-) secretion, and this action was inhibited by AE3-208 but not AE5-599. The response to PGE(2) or acidification in the duodenum was partially attenuated by AE5-599 or AE3-208 alone but completely abolished by the combined administration. Duodenal damage caused by mucosal perfusion with 150 mM HCl for 4 h was worsened by pretreatment with AE5-599 and AE3-208 as well as indomethacin and further aggravated by co-administration of these antagonists. Neither the EP3 nor EP4 antagonist had any effect on the gastric response induced by PGE(2) or acidification. These results clearly demonstrate the involvement of EP3 receptors, in addition to EP4 receptors, in the regulation of duodenal HCO(3)(-) secretion as well as the maintenance of the mucosal integrity of the duodenum against acid injury.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan.
authors.forename: Eitaro
authors.initials: E
authors.lastname: Aihara
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nomura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ise
authors.forename: Kazutomo
authors.initials: K
authors.lastname: Kita
authors.forename: Koji
authors.initials: K
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D009281:Naphthalenes / Q000494:pharmacology; D010654:Phenylbutyrates / Q000494:pharmacology; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C487890:4-(4-cyano-2-(2-(4-fluoronaphthalen-1-yl)propionylamino)phenyl)butyric acid; D001639:Bicarbonates; D009281:Naphthalenes; D010654:Phenylbutyrates; D018078:Receptors, Prostaglandin E; C016767:sulprostone; D015232:Dinoprostone