title: Involvement of prostaglandin E receptor EP3 subtype and prostacyclin IP receptor in decreased acid response in damaged stomach.
abstract: We investigated the roles of cyclooxygenase (COX) isozymes and prostaglandin E (PGE) receptor EP1 and EP3 subtypes or prostacyclin IP receptors in the decrease in acid secretion in the damaged mouse stomach. Male C57/BL6 mice, both wild type and animals lacking EP1, EP3, or IP receptors, were used after 18 h of fasting. Under urethane anesthesia, the stomach was mounted on an ex-vivo chamber and perfused with saline, and acid secretion as well as transmucosal potential difference (PD) was measured before and after exposure to 20 mM taurocholate Na (TC) for 20 min. Indomethacin, SC-560 or rofecoxib was given i.d. 30 min before TC. Mucosal exposure to TC in wild-type mice caused a reduction in PD, followed by decrease in acid secretion. Indomethacin attenuated the decrease in acid secretion after exposure to TC in wild-type mice, an effect mimicked by SC-560 but not rofecoxib, yet none of these drugs affected the decrease in PD. An altered acid response after exposure to TC was similarly observed in EP1 (-/-) mice but mitigated in mice lacking either EP3 or IP receptors, although a decrease in PD was observed in all groups. Furthermore, the decreased acid response was also attenuated by prior administration of the EP3- but not EP1- antagonist. Mucosal levels of PGE(2) and 6-keto PGF(1a) increased after exposure to TC in all groups of mice. In conclusion, the decrease in acid secretion in the damaged stomach is mediated by endogenous PGs derived from COX-1, through PGE(2)/EP3 receptors and prostacyclin/IP receptors.
authors.affiliation: Department of Pharmacology and Experimental Therapeutic, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nishio
authors.forename: S
authors.initials: S
authors.lastname: Terashima
authors.forename: M
authors.initials: M
authors.lastname: Nakashima
authors.forename: E
authors.initials: E
authors.lastname: Aihara
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002208:Caproates / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000032:analysis / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011720:Pyrazoles / Q000494:pharmacology; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013272:Stomach Diseases / Q000378:metabolism* / Q000503:physiopathology; D013450:Sulfones / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology
chemical_list: D001643:Bridged Bicyclo Compounds; D002208:Caproates; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D008565:Membrane Proteins; C122148:ONO 8711; C545648:Ptger3 protein, mouse; C491910:Ptgir protein, mouse; D011720:Pyrazoles; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; C115461:SC 560; D013450:Sulfones; C116926:rofecoxib; D015121:6-Ketoprostaglandin F1 alpha; D013656:Taurocholic Acid; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse; D015232:Dinoprostone; D007213:Indomethacin