人类骨骼肌的乙酰胆碱受体：蛇神经毒素检测到的种属差异。

Acetylcholine receptors of human skeletal muscle: a species difference detected by snake neurotoxins.

作者信息

Ishikawa Y, Kano M, Tamiya N, Shimada Y

出版信息

Brain Res. 1985 Oct 28;346(1):82-8. doi: 10.1016/0006-8993(85)91097-2.

Abstract

The binding abilities of the nicotinic acetylcholine receptors (AChRs) of the skeletal muscles of man and other vertebrates to two typical curaremimetic toxins, erabutoxin b (Eb) and alpha-bungarotoxin (alpha-BT), were investigated. Fluorescent microscopy using rhodamine-labeled erabutoxin b (TMR-Eb) and FITC-labeled alpha-bungarotoxin (FITC-alpha-BT) revealed that AChRs of human and chimpanzee muscles were stained with FITC-alpha-BT, but not with TMR-Eb. In contrast, the AChRs of mouse muscle were stained with both fluorescent toxins. The stainings of human and chimpanzee AChRs with FITC-alpha-BT were inhibited by preincubation with unmodified alpha-BT, but not with either unmodified Eb or other short-chain neurotoxins. Binding experiments using 125I-labeled Eb ([125I]Eb) and 125I-labeled alpha-BT ([125I]alpha-BT) showed that the affinity of human AChRs for [125I]Eb was unusually low. Electrophysiological experiments showed that both acetylcholine potential and end-plate potential of human muscle were blocked by addition of alpha-BT, but not by Eb. On the contrary, acetylcholine potential of rat muscle was blocked by addition of Eb. All these results indicate that AChRs of human and chimpanzee muscles are different from those of other animals in having an exceptionally low affinity for Eb and other short-chain neurotoxins. The results suggest a heterogeneity among vertebrate AChRs concerning their reactivities to curaremimetic toxins.

摘要

研究了人类和其他脊椎动物骨骼肌的烟碱型乙酰胆碱受体（AChRs）与两种典型的箭毒样毒素—— erabutoxin b（Eb）和α-银环蛇毒素（α-BT）的结合能力。使用罗丹明标记的 erabutoxin b（TMR-Eb）和异硫氰酸荧光素标记的α-银环蛇毒素（FITC-α-BT）的荧光显微镜检查显示，人类和黑猩猩肌肉的AChRs被FITC-α-BT染色，但未被TMR-Eb染色。相比之下，小鼠肌肉的AChRs被两种荧光毒素染色。用未修饰的α-BT预孵育可抑制人类和黑猩猩AChRs与FITC-α-BT的染色，但未修饰的Eb或其他短链神经毒素则不能。使用125I标记的Eb（[125I]Eb）和125I标记的α-BT（[125I]α-BT）进行的结合实验表明，人类AChRs对[125I]Eb的亲和力异常低。电生理实验表明，添加α-BT可阻断人类肌肉的乙酰胆碱电位和终板电位，但Eb不能。相反，添加Eb可阻断大鼠肌肉的乙酰胆碱电位。所有这些结果表明，人类和黑猩猩肌肉的AChRs与其他动物的不同，对Eb和其他短链神经毒素的亲和力极低。结果表明脊椎动物AChRs对箭毒样毒素的反应性存在异质性。