PDF(Pubmed)
Abstract：
Muscle relaxants are indispensable for surgical anesthesia. Early studies suggested that a classical non-depolarizing muscle relaxant pancuronium competitively binds to the ligand binding site to block nicotinic acetylcholine receptors (nAChR). Our group recently showed that nAChR which has two distinct subunit combinations are expressed in zebrafish muscles, αβδε and αβδ, for which potencies of pancuronium are different. Taking advantage of the distinct potencies, we generated chimeras between two types of nAChRs and found that the extracellular ACh binding site is not associated with the pancuronium sensitivity. Furthermore, application of either 2 μM or 100 μM ACh in native αβδε or αβδ subunits yielded similar IC50 of pancuronium. These data suggest that pancuronium allosterically inhibits the activity of zebrafish nAChRs.
摘要：
肌肉松弛剂是手术麻醉不可缺少的。早期研究表明，经典的非去极化肌肉松弛剂潘库溴铵竞争性结合配体结合位点以阻断烟碱乙酰胆碱受体（nAChR）。我们的研究小组最近发现，具有两个不同亚基组合的nAChR在斑马鱼肌肉中表达，αβδε和αβδ，潘库溴铵的效力是不同的。利用独特的潜力，我们在两种nAChRs之间产生了嵌合体,发现细胞外ACh结合位点与潘库溴铵敏感性无关.此外，在天然αβδε或αβδ亚基中应用2μM或100μMACh可产生相似的潘库溴铵IC50。这些数据表明潘库溴铵变构抑制斑马鱼nAChR的活性。
