Dual action of prostaglandin E2 on gastric acid secretion through different EP-receptor subtypes in the rat
Dual action of prostaglandin E2 on gastric acid secretion through different EP-receptor subtypes in the rat
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DOI：
10.1152/ajpgi.00397.2004
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发表时间：
2005-07-01
影响因子：
4.5
通讯作者：
Takeuchi, K
中科院分区：
文献类型：
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作者：
Kato, S;Aihara, E;Takeuchi, K
我们研究了前列腺素E(EP)受体亚型在调节大鼠胃酸分泌中的作用。在乌拉坦麻醉下，用生理盐水灌胃，在pH值为7.0的条件下加入50 mM氢氧化钠测定胃酸分泌。静脉输注组胺或五肽胃泌素刺激胃酸分泌。不同的EP激动剂静脉给药，而EP拮抗剂在EP激动剂之前30min或10min皮下注射。PGE(2)对组胺或五肽胃泌素刺激的胃酸分泌均有抑制作用，且呈剂量依赖性。PGE(2)的抑酸作用可被舒前列酮(EP1/EP3激动剂)所模拟，而不能被Butaprost(EP2激动剂)或AE1-329(EP4激动剂)所模拟。在不受EP1拮抗剂ONO-8711影响的情况下，舒前列酮对五肽胃泌素的抑制作用(半数抑制量：3.6mU/kg)强于组胺刺激的胃酸分泌(半数抑制量：18.0mU/kg)。五肽胃泌素增加组胺的腔内释放，这一反应也被舒前列酮抑制。另一方面，AE1-329(EP4激动剂)刺激迷走神经切断动物的胃酸分泌，显著增加鲁米那组胺。这一作用可被西咪替丁和EP4拮抗剂AE3-208完全阻断。这些结果表明，PGE(2)对酸的分泌具有双重作用：通过EP3受体介导的抑制和通过EP4受体的刺激。前者可能通过抑制壁细胞和肠嗜铬细胞发挥作用，而后者可能通过肠嗜铬细胞释放组胺而起作用。
We examined the role of prostaglandin E (EP) receptor subtypes in the regulation of gastric acid secretion in the rat. Under urethane anesthesia, the stomach was superfused with saline, and the acid secretion was determined at pH 7.0 by adding 50 mM NaOH. The acid secretion was stimulated by intravenous infusion of histamine or pentagastrin. Various EP agonists were administered intravenously, whereas EP antagonists were given subcutaneously 30 min or intravenously 10 min before EP agonists. PGE(2) suppressed the acid secretion stimulated by either histamine or pentagastrin in a dose-dependent manner. The acid inhibitory effect of PGE(2) was mimicked by sulprostone (EP1/EP3 agonist) but not butaprost (EP2 agonist) or AE1-329 (EP4 agonist). The inhibitory effect of sulprostone, which was not affected by ONO-8711 (EP1 antagonist), was more potent against pentagastrin(50% inhibition dose: 3.6 mu g/ kg) than histamine-stimulated acid secretion (50% inhibition dose: 18.0 mu g/ kg). Pentagastrin increased the luminal release of histamine, and this response was also inhibited by sulprostone. On the other hand, AE1-329 (EP4 agonist) stimulated the acid secretion in vagotomized animals with a significant increase in luminal histamine. This effect of AE1-329 was totally abolished by cimetidine as well as AE3-208(EP4 antagonist). These results suggest that PGE(2) has a dual effect on acid secretion: inhibition mediated by EP3 receptors and stimulation through EP4 receptors. The former effect may be brought about by suppression at both parietal and enterochromaffin-like cells, whereas the latter effect may be mediated by histamine released from enterochromaffin-like cells.