Gastric ulcerogenic responses following barrier disruption in knockout mice lacking prostaglandin EP1 receptors

K. Takeuchi, Y. Ogawa, S. Kagawa, H. Ukawa

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background/aims: Endogenous prostaglandins (PGs) arc considered to play a pivotal role in maintaining the mucosal integrity of the stomach after injury. In the present study, we evaluated the mucosal ulcerogenic and mucosal blood flow (GMBF) responses in the stomach after damage by taurocholate (TC) in knockout mice lacking EP1 or EP3 receptors. Methods: Under urethane anaesthesia, a mouse stomach was mounted in an ex vivo chamber, exposed to 20 mmol/L TC for 20 min and treated with 20 mmol/L HCl before and after TC. GMBF was measured with a laser Doppler flowmeter. Results: Mucosal exposure to TC in wild-type mice caused a marked decrease in potential difference (PD), followed by an increase in H+ loss and GMBF. The decreased PD was gradually normalized after removal of TC from the chamber, with minimal damage in the mucosa 1 h after TC treatment. This hyperaemic response was inhibited by indomethacin, resulting in severe lesions in the mucosa without any change in PD or H+ loss. None of these responses induced by TC were altered in EP3-/- mice. However, in mice lacking EP1 receptors, TC treatment did not increase GMBF, despite causing PD reduction and acid loss, and resulted in severe damage in the mucosa. These responses were closely similar to those observed in animals pretreated with ONO-8711, a EP1 receptor antagonist. Mucosal PGE2 content was significantly increased after TC, similarly in all groups of mice. Conclusion: These results confirm a mediator role for PGE 2 in gastric hyperaemic response following mucosal exposure to TC and suggest that endogenous PGs may contribute to maintaining mucosal integrity after barrier disruption, mainly through activation of the EP1 receptor subtype.

Original languageEnglish
Pages (from-to)74-82
Number of pages9
JournalAlimentary Pharmacology and Therapeutics, Supplement
Volume16
Issue number2
Publication statusPublished - Apr 1 2002
Externally publishedYes

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Prostaglandin Receptors
Taurocholic Acid
Knockout Mice
Stomach
Mucous Membrane
Prostaglandins
Flowmeters
Urethane
Prostaglandins E
Dinoprostone
Indomethacin
Lasers
Anesthesia

All Science Journal Classification (ASJC) codes

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

Cite this

Gastric ulcerogenic responses following barrier disruption in knockout mice lacking prostaglandin EP1 receptors. / Takeuchi, K.; Ogawa, Y.; Kagawa, S.; Ukawa, H.

In: Alimentary Pharmacology and Therapeutics, Supplement, Vol. 16, No. 2, 01.04.2002, p. 74-82.

Research output: Contribution to journalArticle

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