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MECHANISM OF ACTION OF NOTEXIN AND NOTECHIS 11‐5 ON SYNAPTOSOMES
Author(s) -
Sen I.,
Baba A.,
Schulz R. A.,
Cooper J. R.
Publication year - 1978
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.1471-4159.1978.tb00135.x
Subject(s) - depolarization , synaptosome , acetylcholine , chemistry , choline , biochemistry , calcium , biophysics , neurotoxin , neurochemical , tetrodotoxin , pharmacology , membrane , biology , endocrinology , organic chemistry
The neurochemical activity of notexin and notechis II‐5 was investigated using a synaptosomal preparation of rat cerebral cortices. In preparations preincubated with [ 3 H]choline in order to label acetylcholine, the toxins caused a rapid release of the transmitter which was calcium‐dependent. The toxins were also potent inhibitors of high affinity choline uptake. Both agents produced a marked depolarization of the synaptosomal preparation as measured by a fluorescent dye and at high concentrations lysed the preparation. At a concentration of 0.1 μM, notexin and notechis II‐5 caused a 50% increase in the efflux of lactate dehydrogenase activity. These results, together with electron microscopic observations, indicated that the toxins disrupt the synaptosomal membranes presumably by their inherent phospholipase activity. The release of acetylcholine and inhibition of choline uptake, together with the depolarization of synaptosomal membranes noted in this study, could explain the observed electrophysiological effects of these toxins.