Synthetic peptides of neurotoxins and rabies virus glycoprotein behave as antagonists in a functional assay for the acetylcholine receptor.

Peptides of portions of loop 2 (the "toxic" loop) of snake venom curare-mimetic neurotoxins (alpha-bungarotoxin and king cobra toxin b) and of a structurally similar region of the rabies virus glycoprotein were synthesized. The effect of the peptides on carbachol-induced 22Na+ flux into BC3H-1 cells, which contain nicotinic acetylcholine receptors on their surfaces, was measured. Both the neurotoxin and glycoprotein peptides inhibited ion transport with IC50 values of 10(-4) M to 7 x 10(-7) M. The most effective peptides correspond to neurotoxin loop 2 and inhibited 22Na+ flux in the micromolar range comparable to the competitive antagonist d-tubocurarine. These findings show that neurotoxin loop 2 and the corresponding rabies virus glycoprotein segment interact with the agonist binding site of teh acetylcholine receptor and that short synthetic peptides representing portions of larger molecules by themselves can exert a biological effect on a large macromolecular complex like the acetylcholine receptor.