Yang X, Criswell H E, Breese G R
North Carolina Neurosciences Center, School of Medicine, University of North Carolina at Chapel Hill 27599-7178, USA.
Neurochem Int. 1999 Aug;35(2):185-94. doi: 10.1016/s0197-0186(99)00060-1.
The effect of ethanol on responses to nicotine from rat cerebellar Purkinje neurons was investigated using extracellular single-unit recording. Systemic administration of ethanol initially enhanced the nicotine-induced inhibition from 50% of the Purkinje neurons. However, irrespective of whether there was an initial enhancement, systemic administration of ethanol antagonized the response to nicotine from the majority of Purkinje neurons. When varying ethanol concentrations were electro-osmotically applied to this neuronal cell type, the responses to nicotine (6/8) were enhanced when a low concentration of ethanol (40 mM) was in the pipette, whereas the majority of nicotine responses (10/11) were antagonized when a higher concentration of ethanol (160 mM) was applied to Purkinje neurons. Thus, the concentration of ethanol presented to the neuron seemed to explain the biphasic consequence of systemically administered ethanol on responses to nicotine. In order to determine whether ethanol affected a specific nACh receptor subtype containing the alpha-7 subunit, it was initially established that the nicotinic antagonists, alpha-bungarotoxin (alpha-BTX) and methyllycaconitine (MLA), which are associated with this subunit, had identical actions on responses to nicotine from Purkinje neurons. When MLA was tested against responses to nicotine from this cell type, MLA antagonized the response to nicotine from 45% (9/20) of the neurons tested. In a direct comparison of the action of ethanol to inhibit responses to nicotine with the action of MLA on the same Purkinje neuron, ethanol inhibited responses to nicotine on all neurons sensitive to MLA. However, ethanol also affected nicotine-induced neural changes from some Purkinje neurons not sensitive to MLA antagonism of nicotine. These data support the supposition that ethanol affects a nACh receptor subtype which has an alpha-7 subunit as well as other nACh receptor subtypes without this specific subunit.
采用细胞外单单位记录法研究了乙醇对大鼠小脑浦肯野神经元烟碱反应的影响。全身给予乙醇最初增强了50%的浦肯野神经元对烟碱诱导的抑制作用。然而，无论最初是否有增强作用，全身给予乙醇都会拮抗大多数浦肯野神经元对烟碱的反应。当将不同浓度的乙醇通过电渗作用施加到这种神经元细胞类型时，当移液管中含有低浓度乙醇（40 mM）时，对烟碱的反应（6/8）增强，而当向浦肯野神经元施加较高浓度乙醇（160 mM）时，大多数烟碱反应（10/11）被拮抗。因此，呈现给神经元的乙醇浓度似乎可以解释全身给予乙醇对烟碱反应的双相结果。为了确定乙醇是否影响含有α-7亚基的特定烟碱型乙酰胆碱受体亚型，最初确定与该亚基相关的烟碱拮抗剂α-银环蛇毒素（α-BTX）和甲基lycaconitine（MLA）对浦肯野神经元烟碱反应具有相同作用。当用MLA测试对这种细胞类型烟碱反应时，MLA拮抗了45%（9/20）测试神经元对烟碱的反应。在将乙醇抑制烟碱反应的作用与MLA对同一浦肯野神经元的作用进行直接比较时，乙醇抑制了所有对MLA敏感的神经元对烟碱的反应。然而，乙醇也影响了一些对MLA拮抗烟碱不敏感的浦肯野神经元的烟碱诱导的神经变化。这些数据支持这样的推测，即乙醇影响具有α-7亚基的烟碱型乙酰胆碱受体亚型以及其他没有这种特定亚基的烟碱型乙酰胆碱受体亚型。
