Prostaglandin E Inhibits Indomethacin-Induced Gastric Lesions through EP-1 Receptors
Prostaglandin E Inhibits Indomethacin-Induced Gastric Lesions through EP-1 Receptors
复制标题
前列腺素 E 通过 EP-1 受体抑制吲哚美辛引起的胃损伤
作者：
Keizo Suzuki;H. Araki;H. Mizoguchi;O. Furukawa;K. Takeuchi
背景和目标：我们研究了不同的前列腺素E（PGE）类似物的EP受体亚型对吲哚美辛诱导的大鼠胃病变的影响，并研究了EP受体亚型参与PGE <sub>2</sub>使用EP受体敲除小鼠的保护作用。方法：皮下注射吲哚美辛（35 mg/kg），建立大鼠胃粘膜损伤模型。胃动力测定使用气球的方法，而中性粒细胞趋化性测定使用Boyden室。结果：PGE<sub>2</sub>和阿托品均能明显预防消炎痛引起的胃粘膜损伤，前者的作用可被EP<sub>1</sub>/EP<sub>3</sub>和EP<sub>1所</sub>模拟<sub>，</sub>并可被EP<sub>1</sub>拮抗剂ONO AE 829所拮抗。布他前列素（EP<sub>2</sub>）、ONO-NT-012（EP<sub>3</sub>）和11-脱氧PGE<sub>1</sub>（EP<sub>3</sub>/EP<sub>4</sub>）均未显示对病变的保护作用。吲哚美辛引起胃运动的显着增加，在病变发生之前的反应，并抑制阿托品以及作为EP<sub>1</sub>受体的PGE衍生物。PGE<sub>2</sub>、布他前列素和11-脱氧PGE<sub>1对</sub>中性粒细胞趋化性有轻微的抑制作用，而17-苯基PGE<sub>2</sub>、ONO-NT-012和阿托品对中性粒细胞趋化性均无抑制作用。此外，吲哚美辛在缺乏EP<sub>1</sub>或EP<sub>3</sub>受体的野生型和敲除小鼠中引起的损伤相似，但在野生型和EP<sub>3</sub>受体敲除小鼠中观察到PGE<sub>2</sub>的保护作用，但在缺乏EP<sub>1</sub>受体的小鼠中完全消失。结论：PGE<sub>2</sub>通过EP<sub>1</sub>受体抑制消炎痛诱导的胃损伤，这种作用可能在功能上与抑制胃动力有关，但与抑制中性粒细胞活化/迁移无关。
Backgrounds and Aims: We examined the effect of various prostaglandin E (PGE) analogs specific to EP receptor subtypes on indomethacin-induced gastric lesions in rats and investigated which EP receptor subtype is involved in the protective action of PGE<sub>2</sub> using EP-receptor knockout mice. Methods: Gastric lesions were induced by subcutaneous administration of indomethacin (35 mg/kg). Gastric motility was measured using a balloon method, while neutrophil chemotaxis determined using a Boyden chamber. Results: Indomethacin-induced gastric lesions were significantly prevented by PGE<sub>2</sub> as well as atropine, and the former effect was mimicked by sulprostone (EP<sub>1</sub>/EP<sub>3</sub>) and 17-phenyl PGE<sub>2</sub> (EP<sub>1</sub>) and antagonized by an EP<sub>1</sub> antagonist, ONO-AE-829. Neither butaprost (EP<sub>2</sub>), ONO-NT-012 (EP<sub>3</sub>) nor 11-deoxy PGE<sub>1</sub> (EP<sub>3</sub>/EP<sub>4</sub>) showed any protection on the lesions. Indomethacin caused a marked increase in gastric motility; the response preceded the onset of lesions and was inhibited by atropine as well as PGE derivatives acting as EP<sub>1</sub> receptors. Neutrophil chemotaxis was inhibited by PGE<sub>2</sub>, butaprost and slightly by 11-deoxy PGE<sub>1</sub>, but not by either 17-phenyl PGE<sub>2</sub>, ONO-NT-012 or atropine. In addition, indomethacin caused damage similarly in both wild-type and knockout mice lacking EP<sub>1</sub> or EP<sub>3</sub> receptors, yet the protective action of PGE<sub>2</sub> was observed in wild-type and EP<sub>3</sub> receptor knockout mice but totally disappeared in mice lacking EP<sub>1</sub> receptors. Conclusion: PGE<sub>2</sub> inhibits indomethacin-induced gastric lesions, through EP<sub>1</sub> receptors, and this effect may be functionally associated with inhibition of gastric motility but not of neutrophil activation/migration.
影响因子：
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作者：
GRISHAM, MB;HERNANDEZ, LA;GRANGER, DN
通讯作者：
GRANGER, DN