Takeuchi Koji, Yagi Koji, Kitamura Motohiro, Kubomi Masafumi, Tashima Kim-Ihito
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan.
J Gastroenterol Hepatol. 1998 Nov;13(S3):S221-S226. doi: 10.1111/j.1440-1746.1998.tb01881.x.
We investigated the relationship between prostaglandin E-type receptor (EP receptor) subtypes and gastroduodenal HCO secretion in rats. Under urethane anaesthesia, a stomach mounted in an ex vivo chamber or a proximal duodenal loop was perfused with saline and the HCO secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mmol/L HCl. Prostaglandin E (PGE , i.V.) increased HCO secretion in both the stomach and duodenum; this action was verapamil sensitive and only in the duodenum was potentiated by isobutylmethyl xanthine (IBMX). Duodenal HCO secretion was also stimulated by both sulprostone (EP /EP agonist), enprostil (EP /EP agonist), misoprostol (EP /EP agonist), 11-deoxy PGE (EP /EP agonist) and ONO-NT-012 (EP agonist), but was not affected by either butaprost (EP agonist) or 17-phenyl-ω-trinor-PGE (EP agonist). In contrast, gastric HCO secretion was stimulated by sulprostone, enprostil and 17-phenyl-ω-trinor-PGE , but not by misoprostol, butaprost, 11-deoxy PGE or ONO-NT-012. The EP antagonist SC-51089 inhibited the HCO stimulatory action of sulprostone in the stomach but not in the duodenum. Isobutylmethyl xanthine potentiated the HCO response to sulprostone in the duodenum, while verapamil reduced the response in both the stomach and duodenum. These results suggest that PGE stimulates HCO secretion via different EP receptor subtypes in the stomach and duodenum: in the former the EP receptors linked to Ca and in the latter, the EP receptors coupled with both cAMP and Ca .
我们研究了前列腺素E型受体（EP受体）亚型与大鼠胃十二指肠HCO分泌之间的关系。在氨基甲酸乙酯麻醉下，用生理盐水灌注置于离体腔室中的胃或十二指肠近端肠袢，并使用pH计法在pH 7.0时通过添加10 mmol/L盐酸来测量HCO分泌。前列腺素E（PGE，静脉注射）可增加胃和十二指肠中的HCO分泌；此作用对维拉帕米敏感，且仅在十二指肠中异丁基甲基黄嘌呤（IBMX）可增强该作用。舒前列素（EP/EP激动剂）、恩前列素（EP/EP激动剂）、米索前列醇（EP/EP激动剂）、11-脱氧PGE（EP/EP激动剂）和ONO-NT-012（EP激动剂）也可刺激十二指肠HCO分泌，但布他前列素（EP激动剂）或17-苯基-ω-三降-PGE（EP激动剂）对其无影响。相比之下，舒前列素、恩前列素和17-苯基-ω-三降-PGE可刺激胃HCO分泌，但米索前列醇、布他前列素、11-脱氧PGE或ONO-NT-012则无此作用。EP拮抗剂SC-51089可抑制舒前列素对胃中HCO的刺激作用，但对十二指肠无此作用。异丁基甲基黄嘌呤可增强十二指肠中对舒前列素的HCO反应，而维拉帕米可降低胃和十二指肠中的反应。这些结果表明，PGE通过胃和十二指肠中不同的EP受体亚型刺激HCO分泌：在胃中与Ca相关的EP受体，在十二指肠中与cAMP和Ca均相关的EP受体。
