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Studies on α‐Latrotoxin Receptors in Rat Brain Synaptosomes: Correlation Between Toxin Binding and Stimulation of Transmitter Release
Author(s) -
Meldolesi Jacopo
Publication year - 1982
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.1471-4159.1982.tb06633.x
Subject(s) - stimulation , synaptosome , toxin , receptor , neuroscience , chemistry , biophysics , biology , biochemistry , central nervous system
α‐Latrotoxin (α‐LT), the major component of black widow spider venom, is a high‐molecular‐weight protein that acts presynaptically by stimulating the release of stored neurotransmitters. The purified toxin was iodinated to high specific radioactivity by the Bolton‐Hunter procedure, without appreciable loss of biological activity. By the use of the 125 I‐toxin, specific receptors were revealed in synaptosome fractions isolated from various regions of the rat brain, but not in nonneural tissues. The density of α‐LT receptors [which are probably composed of, or include, membrane protein(s)] varies between 0.6 and 0.88 pmol/mg of synaptosome protein, their affinity is very high ( K A of the order of 10 10 M −1 ), their association rate is fast, and their dissociation rate slow. They might belong to a single, homogeneous class. This last conclusion, however, is still uncertain, because results suggesting a possible heterogeneity were obtained by studying the dissociation of the toxin from synaptosomes incubated in high‐salt buffer. Experiments in which the binding of α‐LT and its dopamine release activity in striatal synaptosomes were investigated in parallel in a variety of experimental conditions support the hypothesis that occupation of the high‐affinity receptors is the initial step in the α‐LT activation of the presynaptic response.