以最小反应模型分析HI-----6抗骨骼肌烟碱受体的作用

Effects of HI 6 on muscle acetylcholine receptor: analysis on minimal reaction model

以最小反应模型分析ＨＩ６抗骨骼肌烟碱受体的作用陈厚昌，白敦衍１，蒋毅萍（第一军医大学药理教研室，１计算机教研室，广州５１０５１５，中国）关键词ＨＩ６；骨骼肌；胆碱能受体；信使ＲＮＡ；非洲爪蟾；卵母细胞目的：研究１（２ｈｙｄｒｏｘｙｉｍｉｎｏｍ...

IM: To study the action of 1 (2 hydroxyimino￣methyl 1 pyridino) 3 (4 carbamoyl 1 pyridino) 2 oxapropane dichloride (HI 6) on skeletal muscle acetylcholine receptor (N 2 ChR). METHODS: N 2 ChR was expressed in Xenopus laevis oocyte after injection with mRNA extracted from denervated rat leg muscles. The inward membrane currents induced by various concentrations of carbamylcholine and effects of HI 6 or d tubocurarine on the currents were measured with voltage clamp technique by fast cell flow of agents. The actions of HI 6 and d tubocurarine on N 2 ChR were analyzed by using the minimal reaction model. RESULTS: K of 40 05, 156 00, and 334 67 μmol·L -1 for HI 6, K of 0 02, 0 10, and 0 18 μmol·L -1 for d tubocurarine were obtained by using the competing for single acetylcholine (ACh) binding site model, the competing for two ACh binding sites model, and the noncompetitive inhibition model, respectively. CONCLUSION: HI 6 and d tubocurarine competed for two ACh binding sites of N 2 ChR with equal affinity to antagonize the effects of the agonist on N 2 ChR. The N 2 ChR inhibition by HI 6 is much weaker than that by d tubocurarine.