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κ-银环蛇毒素:一种神经元烟碱受体拮抗剂与鸡视叶和骨骼肌的结合

kappa-Bungarotoxin: binding of a neuronal nicotinic receptor antagonist to chick optic lobe and skeletal muscle.

作者信息

Wolf K M, Ciarleglio A, Chiappinelli V A

机构信息

Department of Pharmacology, St. Louis University School of Medicine, MO 63104.

出版信息

Brain Res. 1988 Jan 26;439(1-2):249-58. doi: 10.1016/0006-8993(88)91481-3.

DOI:10.1016/0006-8993(88)91481-3
PMID:3359187
Abstract

kappa-Bungarotoxin, a snake venom kappa-neurotoxin, is a potent neuronal nicotinic receptor antagonist. kappa-Neurotoxins are structurally related to the long-type alpha-neurotoxins (including alpha-bungarotoxin), which often fail to block neuronal nicotinic transmission, but which are potent antagonists of nicotinic receptors found on vertebrate skeletal muscle. The binding of kappa-bungarotoxin has now been examined in homogenates of chick skeletal muscle and optic lobe. In muscle, kappa-bungarotoxin binds to nicotinic receptors with 200-fold lower affinity than does alpha-bungarotoxin. The weakest known alpha-neurotoxin, L.s. III, is found to be 6.5-fold more potent than kappa-bungarotoxin. These findings support the conclusion that kappa-neurotoxins are selective for neuronal nicotinic receptors. In the optic lobe, 125I-alpha-bungarotoxin and 125I-L.s. III. A second nicotinic site, detected with high affinity by both alpha-neurotoxins, is only weakly bound by kappa-bungarotoxin. No evidence for a unique 125I-kappa-neurotoxin site is observed. Furthermore, kappa-bungarotoxin does not recognize the high affinity L-[3H]nicotine binding site in chick optic lobe which is distinct from the alpha-neurotoxin binding sites. Three subtypes of nicotinic sites can thus be defined in chick optic lobe, although which of these subtypes is involved in nicotinic transmission in the lobe remains to be conclusively determined.

摘要

κ-银环蛇毒素是一种蛇毒κ-神经毒素,是一种有效的神经元烟碱型受体拮抗剂。κ-神经毒素在结构上与长型α-神经毒素(包括α-银环蛇毒素)相关,后者通常无法阻断神经元烟碱传递,但却是脊椎动物骨骼肌上烟碱型受体的有效拮抗剂。目前已在鸡骨骼肌和视叶匀浆中检测了κ-银环蛇毒素的结合情况。在肌肉中,κ-银环蛇毒素与烟碱型受体的结合亲和力比α-银环蛇毒素低200倍。已知最弱的α-神经毒素L.s. III比κ-银环蛇毒素的效力高6.5倍。这些发现支持了κ-神经毒素对神经元烟碱型受体具有选择性的结论。在视叶中,125I-α-银环蛇毒素和125I-L.s. III。两种α-神经毒素均以高亲和力检测到的第二个烟碱型位点,仅与κ-银环蛇毒素有弱结合。未观察到独特的125I-κ-神经毒素位点的证据。此外,κ-银环蛇毒素不能识别鸡视叶中与α-神经毒素结合位点不同的高亲和力L-[3H]尼古丁结合位点。因此,在鸡视叶中可以定义三种烟碱型位点亚型,尽管这些亚型中哪一种参与视叶中的烟碱传递仍有待最终确定。

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