Endogenous low molecular weight inhibitors of cholinergic binding sites

Endogenous low molecular weight compounds which inhibit ligand binding to nicotinic acetylcholine receptors of neuronal membranes have been isolated from insect nervous tissue. Two distinct heat-stable, cationic inhibitory compounds with molecular weights of about 700-500 Da and below 500 Da have been identified. The active material was found to competitively inhibit ¹²⁵I]α-bungarotoxin and ³H]acetylcholine binding in a reversible, dose dependent manner. Comparative binding studies revealed that the active material also inhibits ¹²⁵I]α-bungarotoxin and ³H]acetylcholine binding in vertebrate brain, but not in the electric tissue of Torpedo. These results suggest that the endogenous inhibitors may function as modulators specific for neuronal acetylcholine receptors.