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Action of anesthetics on acetylcholine receptor and voltage-dependent Na channel in cultured adrenal medullary cells.

麻醉剂对培养的肾上腺髓质细胞中乙酰胆碱受体和电压依赖性钠离子通道的作用。

基本信息

批准号：
62570713
负责人：
SHIGEMATSU Akio
金额：
$ 1.41万
依托单位：
University of Occupational and Environmental Health, School of Medicine.
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

The effects of general anesthetics on several distinct types of ion channels were investigated in cultured bovine adrenal medullary cells. In these cells, our previous studies suggest that carbachol-induced Na influx via nicotinic receptor-ion channel complex or veratridine-induced na influx via voltage-dependent Na channel causes ca influx via voltage-dependeut Ca channel and triggers catecholamine secretion, whereas high concentration of extracellular potassium directly activates voltage-dependent Ca channel without increasing Na influx.1. Phencyclidine inhibited influx of ^<22>Na, ^<45>Ca and secretion of catecholamines caused by carbachol (IC_<50> 7.0 muM) or by veratridine (IC_<50> 60.0 muM). Clinical concentrations of ketamine suppressed carbachol-induced events (IC_<50> 40.0 muM) with less inhibiting veratridine-induced events (IC_<50> 260 muM). droperidol suppressed veratridine-induced events (IC_<50> 34 muM), but less affected carbachol-induced events (IC_<50> >100 muM).2. Phencyclidine, ketamine and droperidol did not alter high concentration of extracellular potassium-induced ^<45>Ca influx and catecholamine secretion.3. Scatchard analysis of [^3H]-phencyclidine specific binding revealed two different equilibrium dissociation constants (4.3 and 77.4 muM). [^3H]-Phencyclidine binding was not inhibited by carbachol, muscarine, d-tubocurarine, hexamethonium, tetrodotoxin, veratridine and -scorpion venom. Droperidol (100 muM) and ketamine (100 muM) reduced [^3H]-phencyclidine binding to 40.3 and 80.1% of control.4.These results indicate that general anesthetics used bind to two distinct classes of sites, each of which is functionally associated with nicotinic receptor-ion channel complex and with voltage-dependent Na channel and inhibit Na influx. Anesthetics do not interfere with voltage-dependent Ca channel, but inhibition of Na influx leads to the reduction of Ca influx and catecholamine secretion caused by carbachol and by veratridine.

在培养的牛肾上腺髓质细胞上观察了全麻药对几种不同类型离子通道的影响。在这些细胞中，我们以前的研究表明，卡巴胆碱通过烟碱受体-离子通道复合体诱导的钠内流或藜芦碱通过电压依赖性钠通道诱导的钠内流引起电压依赖性钙通道的钙内流并激发儿茶酚胺的分泌，而细胞外高浓度的钾直接激活电压依赖性钙通道而不增加钠内流。苯环利定可抑制卡巴胆碱或藜芦碱引起的钙内流和儿茶酚胺的分泌。临床浓度的氯胺酮抑制卡巴胆碱诱导的事件(IC_&lt；50&gt；40.0um)，而对藜芦碱诱导的事件的抑制较少(IC_&lt；50&gt；260um)。氟哌利多抑制藜芦碱诱导的事件(IC_&lt；50；>34 um)，但对卡巴胆碱诱导的事件影响较小(IC_&lt；50；&gt；100 um)。苯环利定、氯胺酮和氟哌利多不改变高浓度钾引起的细胞外钙内流和儿茶酚胺分泌。[~3H]-苯环利定结合的Scatchard分析表明有两个不同的平衡解离常数(4.3和77.4um)。卡巴胆碱、毒僵碱、D-管库拉林、六甲铵、河豚毒素、藜芦碱和-蝎毒不能抑制苯环利定的结合。氟哌利多(100um)和氯胺酮(100um)使[~1H]-苯环利定的结合量分别减少到对照组的40.3%和80.1%。4.这些结果表明，全麻药结合到两类不同的部位，每一种都与烟碱受体-离子通道复合体和电压依赖性钠通道有关，并抑制钠内流。麻醉剂不干扰电压依赖性钙通道，但抑制钠内流可使卡巴胆碱和藜芦碱引起的钙内流和儿茶酚胺分泌减少。