Gastric mucosal protection against ethanol by EP2and EP4signaling through the inhibition of leukotriene C4production
| Autor: | Masataka Majima, Takako Ae, Takashi Ohno, Youichiro Hattori, Katsuharu Arai, Takeo Saeki, Katsunori Saigenji, Sumito Mizuguchi |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Time Factors Physiology Prostaglandin E2 receptor Prostaglandin Pharmacology Dinoprostone Rats Sprague-Dawley chemistry.chemical_compound Venules Physiology (medical) Benzoquinones medicine Animals Receptors Prostaglandin E Vasoconstrictor Agents Lipoxygenase Inhibitors Prostaglandin E2 Arachidonate 5-Lipoxygenase Ethanol Dose-Response Relationship Drug Hepatology Leukotriene C4 Stomach Gastroenterology Receptors Prostaglandin E EP2 Subtype Immunohistochemistry Receptors Prostaglandin E EP1 Subtype Rats Perfusion medicine.anatomical_structure chemistry Eicosanoid Chromones Gastric Mucosa Vasoconstriction Receptors Prostaglandin E EP3 Subtype Immunology Leukotriene Antagonists Signal transduction Receptors Prostaglandin E EP4 Subtype Signal Transduction medicine.drug |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 294:G80-G87 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00292.2007 |
| Popis: | 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. PGE2and 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 PGE2and by EP2and EP4agonists (100 nM) but not by an EP1or an EP3agonist. Ethanol-induced mucosal injury was also inhibited by EP2and EP4agonists. When leukotriene (LT)C4levels in the perfusate of the gastric mucosa were determined by ELISA, intragastric ethanol administration elevated the LTC4levels sixfold from the basal levels. These elevated levels were significantly (60%) reduced by both EP2and EP4agonists but not by other EP agonists. Since LTC4application at the window constricted collecting venules strongly, and an LTC antagonist reduced ethanol-induced mucosal injury, reductions in LTC4generation in response to EP2and EP4receptor signaling may be relevant to the protective action of PGE2. The present results indicate that EP2and EP4receptor signaling inhibits ethanol-induced gastric mucosal injury through cancellation of collecting venule constriction by reducing LTC4production. |
| Databáze: | OpenAIRE |
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