A critical evaluation of the use of toxins from Dendroaspis viridis to block nicotinic responses at central and ganglionic synapses

Abstract

Previous work by other investigators has shown that toxins prepared from Dendroaspis viridis venom block cholinergic transmission at the neuromuscular junction, as well as nicotinic transmission in frog spinal cord and in snail neurons. This suggested that these ligands may be useful for studying nicotinic receptors in the central nervous system. Thus, Dendroaspis viridis venom was fractionated into its toxin components. Only one of the fractions possessed activity as assessed by: (1) inhibition of alpha-bungarotoxin (alpha-BGT) binding at the neuromuscular junction (25% at 50 microgram toxin/ml) or (2) inhibition of the ventral root--dorsal root potential (VR--DRP), a nicotinic response in frog spinal cord. However, in the spinal cord preparation, in addition ot this blockade of the nicotinic pathway, convulsant activity and an increase in the amplitude of other root potentials was observed. Binding experiments using [125I]dendrotoxin demonstrated that the labeled compound bound to central nervous tissue such as brain or spinal cord; this was not displaced by nicotine (10(-4) M) or D-tubocurarine (10 (-4) M), a nicotinic antagonist, indicating either non-specific binding or binding to a non-nicotinic receptor. These results thus suggest that toxins from Dendroaspis viridis venom are not suitable ligands for central nicotinic receptors. In addition, as experiments also demonstrated that the dendrotoxins did not block cholinergic transmission in frog sympathetic ganglia, it contraindicates their use at ganglionic nicotinic receptors.