Crotoxin effects on [formula omitted] cholinergic excitable vesicles and the role of its phospholipase a activity

Abstract

The phospholipolytic neurotoxin from Crotalus durissus terrificus , crotoxin, is able to produce a dose- and time-dependent block of carbachol-stimulated 22Na efflux from pre-loaded Torpedo californica excitable vesicles. The blocking activity is dependent on calcium and is abolished by chemical modification with p-bromophenacyl bromide. The isolated basic subunit, crotoxin B, produces an identical block, whereas the isolated acidic subunit, crotoxin A, has no detectable effect. Neither crotoxin nor crotoxin B antagonizes the binding of [ 125I]-α-bungarotoxin to purified acetylcholine receptor, although, at high concentrations, they antagonize its binding to acetylcholine receptor-rich membrane fragments. Certain phospholipase A 2 enzymes and the fatty acid products of their digestion can mimic the crotoxin action. It is therefore suggested that, although considered a pre-synaptic neurotoxin, crotoxin can have in vitro post-synaptic effects, possibly mediated by its endogeneous phospholipase A 2 activity.