Isolation and Characterization of Presynaptically Acting Neurotoxins from the Venom of Bungarus Snakes

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Abstract
Five presynaptic toxins were isolated in pure form from the venom of B. multicinctus and B. caeruleus and named .beta.1, .beta.2, .beta.3, .beta.4 and .beta.-ceruleotoxin. They differ in electrophoretic mobility and amino acid composition, while all have the same MW (22,000) and are composed of 2 subunits of MW 9000 and 12,000. The toxins have phospholipase A activity when assayed with both natural and synthetic phospholipids, and this activity requires the presence of Ca2+. .beta.-Bungarotoxin (.beta.3) binds 1 mol of Ca2+/mol of protein and this binding induces a conformational change as detected by fluorescence measurements in the presence of the dye 8-anilino-1-napthalene sulfonic acid. The phospholipase activity of all the toxins is lost when a critical histidine residue is modified with p-bromophenacyl bromide. As a result of the modification the lethality of the toxins is greatly reduced. Native toxin causes a rapid decrease in amplitude of end-plate potentials, followed by a transient increase and subsequent decrease, until transmitter release is completely abolished. The modified toxin still causes the early decrease in release but toxin action does not progress to complete block. The rate of blockage of transmitter release by native toxin is reduced in the presence of modified toxin. Phospholipase activity plays an important role in the action of this class of toxins at the neuromuscular junction.