THE MECHANISM OF ACTION OF β‐BUNGAROTOXIN
THE MECHANISM OF ACTION OF β‐BUNGAROTOXIN
复制标题
β-金环蛇毒素的作用机制
DOI：
10.1111/j.1471-4159.1975.tb04354.x
复制
发表时间：
1975
影响因子：
4.7
通讯作者：
B. Howard
中科院分区：
文献类型：
--
作者：
J. Wernicke;A. D. Vanker;B. Howard
-β - Bungarotoxin是一种突触前作用的多肽神经毒素，可引起突触体中先前积累的γ -氨基丁酸和2 -脱氧- d -葡萄糖的外排。毒素诱导的γ -氨基丁酸外排是Na+依赖性过程，而2 -脱氧葡萄糖外排是Na+非依赖性过程。用低分子量化合物（包括抑制氧化磷酸化的脂肪酸）处理突触体也能产生这些效果。用β‐班加罗毒素孵育后，突触体显示出[U‐14C]葡萄糖产生14CO2的增加和ATP水平的降低。β‐Bungarotoxin对各种亚细胞膜组分进行处理，当添加到线粒体中时，会产生一种因子来解偶联氧化磷酸化。毒素处理脑组织的线粒体对底物的最大利用率受到限制。我们得出结论，β‐班加罗毒素通过抑制神经末梢线粒体的氧化磷酸化起作用。这种抑制解释了观察到的β -班加罗毒素对突触体和神经肌肉连接处的影响。我们认为对能量代谢的影响是由发现与毒素相关的磷脂酶a活性引起的。
—β‐Bungarotoxin, a presynaptically‐acting polypeptide neurotoxin, caused an efflux from synaptosomes of previously accumulated γ‐aminobutyric acid and 2‐deoxy‐d‐glucose. The toxin‐induced efflux of γ‐aminobutyric acid occurred by a Na+ ‐dependent process while that of 2‐deoxyglucose was Na+ ‐independent. These effects were also produced by treating synaptosomes with low molecular weight compounds, including fatty acids, that inhibit oxidative phosphorylation. After incubation with β‐bungarotoxin, synaptosomes exhibited increased production of 14CO2 from [U‐14C]glucose and decreased ATP levels. β‐Bungarotoxin treatment of various subcellular membrane fractions caused the production of a factor that uncoupled oxidative phosphorylation when added to mitochondria. Mitochondria from toxin‐treated brain tissue exhibited a limitation in the maximal rate of substrate utilization. We conclude that β‐bungarotoxin acts by inhibiting oxidative phosphorylation in the mitochondria of nerve terminals. This inhibition accounts for the observed β‐bungarotoxin effects on synaptosomes and at neuromuscular junctions. We suggest that the effects on energy metabolism result from a phospholipase A activity found to be associated with the toxin.