Biochemical Characterization of the Nicotinic Cholinergic Receptors in Human Brain: Binding of (—)‐[3H]Nicotine

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Abstract
L-[3H]Nicotine was specifically bound to membranes of human brains obtained at autopsy. The binding was stereospecific, (-)-nicotine being 40 times more potent than (+)-nicotine in displaying labeled (-)-nicotine. Saturation binding studies revealed the presence of 2 binding sites with dissociation constant (Kd) values of 8.1 and 86 nM and maximum binding capacity (Bmax) values of 36 and 90 fmol/mg protein, respectively. In competition studies, nicotine agonists were 1000 times more potent than ganglionic, neuromuscular and muscarine blocking drugs in displacing labeled (-)-nicotine. IC50 [concentration producing 50% inhibition] values for cholinergic drugs of (-)-[3H]nicotine binding were as follows: (-)-nicotine, 0.51 nM; acetylcholine, 12.6 nM; (+)-nicotine, 19.9 nM; cytisine, 27.3 nM; and carbachol, 527 nM. IC50 values of .alpha.-bungarotoxin, hexamethonium, d-tubocurarine and atropine were > 50 .mu.M. (-)-[3H]-nicotine binding was highest in the nucleus basalis of Meynert and thalamus and lowest in the cerebral cortex and caudate in the brain regions tested. Nicotinin cholinergic receptors are evidently present in human brain and that there are regional differences in the density of these receptors.