Nicotinic cholinergic receptors in brain synaptosomes.

In order to elucidate pharmacological characteristics of nicotinic receptors in the brain, competitive binding of nicotine analogues or cholinergic agents to brain particles was studied utilizing [3H]nicotine. The binding of [3H]nicotine to brain crude nitochondrial or synaptosomal fraction was progressively inhibited by the addition of increasing amounts of native nicotine or nornicotine, but cotinine had little effect. Of the myelin, synaptosomal and mitochondrial subfractions of the crude mitochondrial fraction, [3H]nicotine binding was almost exclusively confined to synaptosomes. In this binding, the affinity constant was 1.97 X 10(9)/M and the maximum binding capacity was 7.30 X 40(-8) M/g of protein. This binding was reduced by 50% in the presence of 4 X 10(-7) M D-tubocurarine and 10(-6) M carbamylcholine, while atropine was the least effective of the drugs tested. These findings suggest the possible existence of nicotinic cholinergic receptors in the synaptic region. A study of regional differences in nicotinic cholinergic receptors showed that higher specific bindings of nicotine to synaptosomes occurred in the hypothalamus, hippocampus and thalamus. These findings suggest that the nicotinic cholinergic mechanism plays an important role in these regions of the central nervous system.