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The Action of Black Widow Spider Venom on Cholinergic Mechanisms in Synaptosomes
Author(s) -
Baba Akemichi,
Cooper Jack R.
Publication year - 1980
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.1471-4159.1980.tb11217.x
Subject(s) - venom , chemistry , acetylcholine , depolarization , tetrodotoxin , synaptosome , snake venom , tris , pharmacology , biochemistry , biophysics , chromatography , biology , membrane
Black widow spider venom (BWSV) promoted the massive release of labeled acetylcholine from synaptosomes and in addition, inhibited high‐affinity choline uptake into the preparation. Both activities occurred in the absence of [Ca 2+ ] 0 . When Na + in Krebs‐Ringer was replaced isotonically by sucrose, BWSV did not cause any release of [ 3 H]ACh. On the other hand, BWSV was still effective if Na + was replaced by lithium, glucosamine, or Tris. Tetrodotoxin (10 −5 M) failed to prevent the ACh‐releasing action of the venom. The uptake of [ 3 H]norepinephrine and [ 3 H]tyrosine into the P 2 fraction was significantly inhibited by BWSV pretreatment. However, the effect of the venom on the uptake of [ 3 H]deoxyglucose was slight. In addition, the venom‐induced release of [ 3 H]norepinephrine was much higher than that of [ 3 H]deoxyglucose. The change in membrane potential of the preparation in duced by BWSV as examined using the voltage‐sensitive fluorescence probe, 3, 3′‐dipentyl‐2, 2′‐oxacarbocyanine. BWSV pretreatment markedly increased the synaptosomal fluorescence, indicating a depolarization of the preparation. This action of the venom was also observed in a Ca 2+ ‐free or K + ‐free medium, but could be blocked by pretreatment with antivenom. Pretreatment of the P 2 fraction with concanavalin A completely blocked the action of BWSV. Also, the BWSV failed to promote the release of transmitter if the venom was prein‐cubated with a low concentration of purified gangliosides. Even after prolonged treatment with high concentrations of BWSV, an electron microscopic study showed no depletion of the synaptic vesicles in presynaptic terminals of the cortical P 2 preparations or striatal slices. It is suggested that the venom expresses its activity by binding to glycoproteins and/or gangliosides on the synaptic membrane, opening a cation channel. The subsequent depolarization then inhibits uptake processes and promotes transmitter release that is independent of external calcium.