Bale Ambuja S, Smothers Corigan T, Woodward John J
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia, VA 23298, USA.
Br J Pharmacol. 2002 Oct;137(3):375-83. doi: 10.1038/sj.bjp.0704874.
1 Toluene is a representative example of a class of industrial solvents that are voluntarily inhaled as drugs of abuse. Previous data from this lab and others has shown that toluene modulates the function of N-methyl-D-aspartate (NMDA), gamma-aminobutyric acid (GABA) and glycine receptors at concentrations that do not affect non-NMDA receptors. 2 We utilized two-electrode voltage-clamp and whole cell patch-clamp techniques to assess the effects of toluene on neuronal nicotinic acetylcholine receptors expressed in oocytes and cultured hippocampal neurons. Toluene (50 micro M to 10 mM) produced a reversible, concentration-dependent inhibition of acetylcholine-induced current in Xenopus oocytes expressing various nicotinic receptor subtypes. The alpha4beta2 and alpha3beta2 subunit combinations were significantly more sensitive to toluene inhibition than the alpha4beta4, alpha3beta4 and alpha7 receptors. 3 Receptors composed of alpha4 and beta2(V253F) subunits showed alpha4beta4-like toluene sensitivity while those containing alpha4 and beta4(F255V) subunits showed alpha4beta2-like sensitivity. 4 In hippocampal neurons, toluene (50 micro M to 10 mM) dose-dependently inhibited ACh-mediated responses with an IC(50) of 1.1 mM. 5 Taken together, these results suggest that nicotinic receptors, like NMDA receptors, show a subunit-dependent sensitivity to toluene and may represent an important site of action for some of the neurobehavioural effects of toluene.
1 甲苯是一类被作为滥用药物而自愿吸入的工业溶剂的典型代表。该实验室及其他机构之前的数据表明，甲苯在不影响非N-甲基-D-天冬氨酸（NMDA）受体的浓度下，可调节NMDA、γ-氨基丁酸（GABA）和甘氨酸受体的功能。2 我们利用双电极电压钳和全细胞膜片钳技术，评估甲苯对卵母细胞和培养的海马神经元中表达的神经元烟碱型乙酰胆碱受体的影响。甲苯（50微摩尔至10毫摩尔）对表达各种烟碱型受体亚型的非洲爪蟾卵母细胞中乙酰胆碱诱导的电流产生可逆的、浓度依赖性抑制。α4β2和α3β2亚基组合对甲苯抑制的敏感性明显高于α4β4、α3β4和α7受体。3 由α4和β2（V253F）亚基组成的受体表现出类似α4β4的甲苯敏感性，而含有α4和β4（F255V）亚基的受体则表现出类似α4β2的敏感性。4 在海马神经元中，甲苯（50微摩尔至10毫摩尔）剂量依赖性地抑制乙酰胆碱介导的反应，半数抑制浓度（IC50）为1.1毫摩尔。5 综上所述，这些结果表明，烟碱型受体与NMDA受体一样，对甲苯表现出亚基依赖性敏感性，可能是甲苯某些神经行为效应的重要作用位点。
