Depoortere I, Peeters T L
Department of Medical Research, Katholieke Universiteit Leuven, Belgium.
Regul Pept. 1995 Feb 14;55(3):227-35. doi: 10.1016/0167-0115(94)00111-a.
The present study was undertaken to explore motilin's transduction pathway in the rabbit. Guanine nucleotides inhibited 125I-motilin binding in rabbit antral tissue and increased the dissociation of motilin from its receptor. Motilin, the motilin agonist erythromycin A enol ether (EM-201) and carbachol (taken as control) increased the production of inositol phosphates in rabbit duodenal smooth muscle strips labeled with myo-[2-3H]inositol. The effect of carbachol was blocked by atropine. Dose-response curves revealed that 50% of this effect was obtained with 3.9 nM motilin, 170 nM EM-201, 0.54 microM carbachol. Chromatographic separation of the inositol phosphate metabolites showed significant increases in the levels of [3H]inositol bisphosphate and of [3H]inositol trisphosphate. The three substances were without effect upon the metabolism of cAMP, nor did they modulate the rise in cAMP induced by GTP. We propose that motilin's transduction pathway uses a G protein that causes an increase in inositol trisphosphate which is rapidly metabolized, and which may release calcium from intracellular stores.
本研究旨在探索胃动素在兔体内的转导途径。鸟嘌呤核苷酸抑制兔胃窦组织中125I-胃动素的结合，并增加胃动素与其受体的解离。胃动素、胃动素激动剂红霉素A烯醇醚（EM-201）和卡巴胆碱（作为对照）增加了用肌醇-[2-3H]标记的兔十二指肠平滑肌条中肌醇磷酸的产生。卡巴胆碱的作用被阿托品阻断。剂量反应曲线显示，3.9 nM胃动素、170 nM EM-201、0.54 μM卡巴胆碱可产生50%的这种效应。肌醇磷酸代谢产物的色谱分离显示，[3H]肌醇二磷酸和[3H]肌醇三磷酸水平显著升高。这三种物质对cAMP的代谢没有影响，也不调节由GTP诱导的cAMP升高。我们提出，胃动素的转导途径使用一种G蛋白，该蛋白导致肌醇三磷酸增加，肌醇三磷酸迅速代谢，并可能从细胞内储存中释放钙。
