title: Prostaglandin E receptor EP1 subtype but not prostacyclin IP receptor involved in mucosal blood flow response of mouse stomachs following barrier disruption.
abstract: OBJECTIVE
  We investigated the role of prostacyclin IP receptors in gastric mucosal protection as well as functional responses induced by taurocholate Na (TC) as a mild irritant using IP receptor knockout mice, in comparison with prostaglandin (PG) E receptor EP1 subtype knockout animals.
  
  
  METHODS
  Male C57/BL6 mice fasted for 18 h were used under urethane anesthesia. The stomach mounted on an ex vivo chamber was perfused with 20 mM HCl, and the transmucosal potential difference (PD), luminal acid loss, and gastric blood flow (GMBF) were simultaneously measured before and after exposure of the stomach to 20 mM TC for 20 min.
  
  
  RESULTS
  Mucosal exposure to TC in wild-type mice caused a marked decrease in PD, followed by an increase in H(+) loss and GMBF. The PD gradually normalized after removal of TC from the chamber, with minimal damage in the mucosa 1 h later. The increase of GMBF following TC treatment was inhibited by indomethacin with no change in PD reduction or H(+) loss, resulting in severe lesions in the mucosa. None of these responses induced by TC were significantly altered in IP receptor knockout mice. However, in mice lacking EP1 receptors, TC did not increase GMBF, despite causing PD reduction and acid loss, and resulted in severe damage in the mucosa. Mucosal PGE(2) levels were significantly increased after TC, similarly, in all groups of mice, while levels of 6-keto-PGF(1alpha) showed a slight but not significant increase in all groups.
  
  
  CONCLUSIONS
  We confirmed the importance of endogenous PGs and EP1 receptors in the adaptive protection and functional responses induced by a mild irritant in mouse stomach and further suggested that IP receptors are not actively involved in maintaining the gastric mucosal integrity under adverse conditions.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Komoike
authors.forename: Masato
authors.initials: M
authors.lastname: Nakashima
authors.forename: Akari
authors.initials: A
authors.lastname: Nakagiri
authors.forename: Koji
authors.initials: K
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D044006:Receptors, Epoprostenol / Q000502:physiology*; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D012039:Regional Blood Flow; D013656:Taurocholic Acid / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D002756:Cholagogues and Choleretics; D044006:Receptors, Epoprostenol; D018078:Receptors, Prostaglandin E; D013656:Taurocholic Acid