Biochemical and electrophysiological demonstrations of the actions of beta-bungarotoxin on synapses in brain.
Homogeneous beta-bungarotoxin interacts irreversibly with rat olfactory cortex and produced permanent inhibition of neurotransmission (half-time of blockade for 230 nM toxin in 25 min). Binding occurs in the absence of divalent cations, but the rate of synaptic blockade is increased by Ca2+, which activates the intrinsic phospholipase A2 activity of the toxin. Other observable actions of the toxin, seen with rat cerebrocortical synaptosomes, are an increase in the release of acetylcholine, glutamate and gamma-aminobutyrate and impairment of transmitter uptake, which are all insensitive to tetrodotoxin. Inactivation of the toxin's phospholipase activity by chemical modification with p-bromophenacyl bromide diminishes the observed concomitant efflux of the neurotransmitters and lactate dehydrogenase. Collectively, the results support the idea that the toxin binds specifically and irreversibly to component(s) on nerve terminals and this together with the resultant phospholipolysis leads eventually to synaptic blockade. Such a proposal would account for the unique toxicity of the protein relative to phospholipase A2 enzymes.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000502:physiology*; D002038:Bungarotoxins / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D004594:Electrophysiology; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D009830:Olfactory Bulb / Q000502:physiology; D010741:Phospholipases A / Q000502:physiology; D054467:Phospholipases A2; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002038:Bungarotoxins; D005971:Glutamates; D018698:Glutamic Acid; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D010741:Phospholipases A; D054467:Phospholipases A2; D000109:Acetylcholine; D002118:Calcium