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The effects of muscle relaxants on adult-type and fetal-type nictinic acetylcholine receptors

肌松剂对成人型和胎儿型烟碱型乙酰胆碱受体的影响

基本信息

批准号：
09671566
负责人：
YAMADA Yasue
金额：
$ 2.24万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671566/
关键词：
Nicotinic acetylcholine receptor Neuromuscular junction Acetylcholine Succinylcholine Muscle relaxants Xenopus oocytes synthetic RNA Two electrode voltage clamp アフリカツメガエル

项目摘要

The effects of agonists and competitive antagonists on bovine muscle adult- (junctional) and fetal-type (extrajunctional) bovine muscle nicotinic acetylcholine receptors (nAChR) have been compared by using Xenopus oocyte expression system, and the following results were obtained.1. The Km values of the adult-type nAChR for acetylcholine (ACh) and succinyicholine (SCh) were not significantly different from those of the fetal-type The adult-type nAChR showed a faster time constant of current decay than the fetal-type did at 300 muM of ACh or SCh, when the currents were approximated by a single exponential function (p<0.05). At 1 mM, SCh exerted a potent blocking action of the open ion channel.2. In double pulse experiments, the recovery from the desensitized state after application of ACh or SCh was faster in the case of the fetal-type nAChR than in the adult-type. tau_<rec> (the time constant of recovery from desensitization) of SCh was slower than that of ACh on both nAChRs. tau_<rec> at 10 muM of SCh was almost the same as that at 100 muM of ACh. These results suggest that the neuromuscular blockade caused by SCh is due to the slow rate of recovery from desensitization and that the difference between adult- and fetal-type nAChR is responsible for different desensitized states.3. The Ki value of the adult-type nAChR for vecuronium, a competitive antagonist for nAChRs, was smaller than that of the fetal-type. When the sequence of addition and washout of ACh was repeated in the presence of vecuronium or beta-tubocurarine, both nAChRs showed remarkable difference in restoration of ACh- evoked currents and the adult-type showed the reduced response. These results suggest that a fraction of the channel blockade by vecuronium or beta-tubocurarine was borne in the non-competitive manner and the fraction appears to be large in the adult-type nAChR.

利用非洲爪蟾卵母细胞表达系统，比较了激动剂和竞争性拮抗剂对牛肌肉成熟型（连接型）和胎儿型（连接外型）牛肌肉烟碱乙酰胆碱受体（nAChR）的作用，得到以下结果.成人型nAChR对乙酰胆碱（ACh）和琥珀胆碱（SCh）的Km值与胎儿型无显著差异。当ACh或SCh浓度为300 μ M时，成人型nAChR的电流衰减时间常数比胎儿型快（p<0.05）。在1 mM时，SCh对开放离子通道有强的阻断作用.在双脉冲实验中，从应用ACh或SCh后的脱敏状态的恢复速度更快的情况下，胎儿型nAChR比成人型。在<rec>两种nAChR上，SCh的tau_（脱敏恢复时间常数）均比ACh慢。在<rec>10 μ M SCh和100 μ M ACh时，tau_2几乎相同。这些结果表明，SCh引起的神经肌肉阻滞是由于从脱敏中恢复的缓慢速率，成人型和胎儿型nAChR之间的差异是导致不同脱敏状态的原因.成人型nAChR对nAChR竞争性拮抗剂维库溴铵的Ki值小于胎儿型nAChR。当在维库溴铵或β-筒箭毒碱存在下重复ACh的加入和洗脱顺序时，两种nAChRs在ACh诱发电流的恢复方面表现出显着差异，成人型表现出降低的反应。这些结果表明，维库溴铵或β-筒箭毒碱的通道阻滞的一部分是承担在非竞争性的方式和分数似乎是大的成人型nAChR。