Studies on α-latrotoxin receptors in rat brain synaptosomes: Correlation between toxin binding and stimulation of transmitter release

J. Meldolesi

Research output: Contribution to journalArticlepeer-review

Abstract

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 neurotransmitter. 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 125I-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 1010 M-1), their assocition 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.

Original languageEnglish
Pages (from-to)1559-1569
Number of pages11
JournalJournal of Neurochemistry
Volume38
Issue number6
Publication statusPublished - 1982

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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