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THE MECHANISM OF ACTION OF β‐BUNGAROTOXIN
Author(s) -
Wernicke J. F.,
Vanker A. D.,
Howard B. D.
Publication year - 1975
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1975.tb04354.x
Subject(s) - oxidative phosphorylation , neurotoxin , mitochondrion , biochemistry , synaptosome , toxin , bungarotoxin , phosphorylation , uncoupling agents , chemistry , dinitrophenol , biology , efflux , atpase , incubation , enzyme , membrane , nicotinic agonist , receptor
—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 14 CO 2 from [U‐ 14 C]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.