Weiss D J, Gurpide E
Department of Pharmacology, Mt. Sinai School of Medicine, City University of New York, New York 10029.
Endocrinology. 1988 Aug;123(2):981-90. doi: 10.1210/endo-123-2-981.
Addition of the cholinergic agents acetylcholine or carbamylcholine (CCh) to suspensions of human endometrial adenocarcinoma cells (Ishikawa line) preincubated with [3H] myoinositol promoted a rapid concentration-dependent hydrolysis of labeled phosphoinositides to inositol tris-, bis-, and monophosphates with EC50 values (mean +/- SE) of 3.5 +/- 1.6 and 26.5 +/- 4.8 microM, respectively. Atropine inhibition of the CCh effects (Ki = 1.6 +/- 1.3 nM) and the ineffectiveness of nicotinic antagonists indicate involvement of a muscarinic receptor. Both basal and CCh-stimulated production of inositol phosphates were higher in the presence of LiCl. The effect of LiCl on inositol monophosphate accumulation was concentration dependent (1-100 mM). Vasopressin, oxytocin, phenylephrine, histamine, and prostaglandin F2 alpha, had no apparent affect on inositol phosphate levels. Phorbol esters inhibited up to 35% of the effect of CCh on inositol phosphate accumulation. Triphenylethylene antiestrogens at micromolar concentrations increased inositol phosphate accumulation, but inhibited the effects of CCh. However, the rapid uptake of trypan blue observed after exposure to 10 microM tamoxifen suggests an alteration of the plasma membrane which may affect signal-transducing systems. The effects of CCh on the production of inositol phosphates and the expected concomitant liberation of diacylglycerol by transformed epithelial cells of human endometrium are of potential significance in normal endometrial physiology, since cholinergic innervation of endometrial glands has been reported, and the role of hormonally stimulated phosphoinositide hydrolysis in secretory mechanisms has been demonstrated in many systems.
向预先用[3H]肌醇孵育的人子宫内膜腺癌细胞（Ishikawa系）悬液中添加胆碱能药物乙酰胆碱或氨甲酰胆碱（CCh），会促使标记的磷酸肌醇迅速发生浓度依赖性水解，生成肌醇三磷酸、二磷酸和单磷酸，其半数有效浓度（EC50值，均值±标准误）分别为3.5±1.6微摩尔和26.5±4.8微摩尔。阿托品对CCh效应的抑制作用（抑制常数Ki = 1.6±1.3纳摩尔）以及烟碱拮抗剂无效，表明存在毒蕈碱受体参与其中。在存在氯化锂的情况下，基础状态下和CCh刺激的肌醇磷酸生成均较高。氯化锂对肌醇单磷酸积累的影响呈浓度依赖性（1 - 100毫摩尔）。加压素、催产素、去氧肾上腺素、组胺和前列腺素F2α对肌醇磷酸水平无明显影响。佛波酯可抑制高达35%的CCh对肌醇磷酸积累的作用。微摩尔浓度的三苯乙烯类抗雌激素药物会增加肌醇磷酸积累，但会抑制CCh的作用。然而，暴露于10微摩尔他莫昔芬后观察到锥虫蓝的快速摄取，提示质膜发生改变，这可能会影响信号转导系统。CCh对人子宫内膜转化上皮细胞肌醇磷酸生成以及预期伴随的二酰基甘油释放的影响，在正常子宫内膜生理学中具有潜在意义，因为已有报道子宫内膜腺体存在胆碱能神经支配，并且在许多系统中已证实激素刺激的磷酸肌醇水解在分泌机制中的作用。
