| Autor: |
Hattori, Youichiro, Ohno, Takashi, Ae, Takako, Saeki, Takeo, Arai, Katsuharu, Mizuguchi, Sumito, Saigenji, Katsunori, Majima, Masataka |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Gastrointestinal & Liver Physiology; Jan2008, Vol. 294, pG80-G87, 8p, 9 Graphs |
| Abstrakt: |
Prostaglandin (PG)E derivatives are widely used for treating gastric mucosal injury. PGE receptors are classified into four subtypes, EP1, EP2, EP3, and EP4. We have tested which EP receptor subtypes participate in gastric mucosal protection against ethanol-induced gastric mucosal injury and clarified the mechanisms of such protection. The gastric mucosa of anesthetized rats was perfused at 2 ml/min with physiological saline, agonists for EP1, EP2, EP3, and EP4, or 50% ethanol, using a constant-rate pump connected to a cannula placed in the esophagus. The gastric microcirculation of the mucosal base of anesthetized rats was observed by transillumination through a window made by removal of the adventitia and muscularis externa. PGE2 and subtype-specific EP agonists were applied to the muscularis mucosae at the window. Application of 50% ethanol dilated the mucosal arterioles and constricted the collecting venules. Collecting venule constriction by ethanol was completely inhibited by PGE2 and by EP2 and EP4 agonists (100 nM) but not by an EP1 or an EP3 agonist. Ethanol-induced mucosal injury was also inhibited by EP2 and EP4 agonists. When leukotriene (LT)C4 levels in the perfusate of the gastric mucosa were determined by ELISA, intragastric ethanol administration elevated the LTC4 levels sixfold from the basal levels. These elevated levels were significantly (60%) reduced by both EP2 and EP4 agonists but not by other EP agonists. Since LTC4 application at the window constricted collecting venules strongly, and an LTC antagonist reduced ethanol-induced mucosal injury, reductions in LTC4 generation in response to EP2 and EP4 receptor signaling may be relevant to the protective action of PGE2. The present results indicate that EP2 and EP4 receptor signaling inhibits ethanol-induced gastric mucosal injury through cancellation of collecting venule constriction by reducing LTC4 production. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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