alpha-Conotoxins selectively inhibit one of the two acetylcholine binding sites of nicotinic receptors.
alpha-Conotoxins selectively inhibit one of the two acetylcholine binding sites of nicotinic receptors.
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DOI：
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发表时间：
1995-07
影响因子：
3.6
通讯作者：
D. Groebe;J. Dumm;E. Levitan;S. Abramson
中科院分区：
文献类型：
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作者：
D. Groebe;J. Dumm;E. Levitan;S. Abramson
肌肉亚型的烟碱乙酰胆碱受体含有两个乙酰胆碱结合位点，可以区分。本文研究了几种α-芋螺毒素对BC_3H_1细胞和电鳐电器烟碱受体上两个乙酰胆碱结合位点的亲和力。α-芋螺毒素MI、GI和SIA均以两种不同且独立的亲和力抑制125 I-α-银环蛇毒素与BC 3 H1细胞上的烟碱乙酰胆碱受体的结合，其差异大于10，000倍。α-芋螺毒素SI和SII的亲和力显著较低，并且这些毒素中的每一种对两个位点的亲和力的差异< 400倍。α-芋螺毒素MI、GI、SIA和SI对来自BC 3 H1细胞的烟碱受体的α/δ亚基界面附近的乙酰胆碱结合位点具有较高的亲和力。然而，当使用来自电鳐电器官的烟碱受体进行评估时，α-芋螺毒素MI对α/γ亚基界面附近的乙酰胆碱结合位点显示出更高的亲和力。这些观察结果表明，物种的γ和δ亚基的序列的变化，导致在一个戏剧性的逆转的相对亲和力的α-芋螺毒素的每个乙酰胆碱结合位点。一些这些意见的实际影响进行了讨论。
Muscle subtypes of the nicotinic acetylcholine receptor contain two acetylcholine binding sites that can be distinguished pharmacologically. The affinities of several alpha-conotoxins for the two acetylcholine binding sites on nicotinic receptors from BC3H1 cells and Torpedo electric organ were investigated. alpha-Conotoxins MI, GI, and SIA each inhibited the binding of 125I-alpha-bungarotoxin to nicotinic acetylcholine receptors on BC3H1 cells with two distinct and independent affinities, which differed by > 10,000-fold. The affinities of alpha-conotoxins SI and SII were significantly lower and the differences in the affinities of each of these toxins for the two sites were < 400-fold. alpha-Conotoxins MI, GI, SIA, and SI had higher affinity for the acetylcholine binding site near the alpha/delta subunit interface of nicotinic receptors from BC3H1 cells. However, when assessed using nicotinic receptors from Torpedo electric organ, alpha-conotoxin MI displayed higher affinity for the acetylcholine binding site near the alpha/gamma subunit interface. These observations suggest that species variations in the sequences of the gamma and delta subunits resulted in a dramatic reversal of the relative affinities of the alpha-conotoxins for each acetylcholine binding site. Some of the practical implications of these observations are discussed.