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Biochemical Characterization of the Nicotinic Cholinergic Receptors in Human Brain: Binding of (—)‐[ 3 H]Nicotine
Author(s) -
Shimohama Shun,
Taniguchi Takashi,
Fujiwara Motohatsu,
Kameyama Masakuni
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb04029.x
Subject(s) - hexamethonium , nicotine , nicotinic agonist , cytisine , acetylcholine receptor , cholinergic , muscarinic acetylcholine receptor , chemistry , carbachol , nucleus basalis , endocrinology , binding site , receptor , nicotinic antagonist , medicine , acetylcholine , dissociation constant , pharmacology , biochemistry , biology , cholinergic neuron
(−)‐[ 3 H]Nicotine was found to bind specifically to membranes of human brains obtained at autopsy. The binding was stereospecific, (−)‐nicotine being 40 times more potent than (+)‐nicotine in displacing labeled (−)‐nicotine. Saturation binding studies revealed the presence of two binding sites with dissociation constant ( K D ) values of 8.1 and 86 n M , and maximum binding capacity ( B max ) values of 36 and 90 fmol/mg protein, respectively. In competition studies, nicotinic agonists were 1,000 times more potent than ganglionic, neuromuscular, and muscarinic blocking drugs in displacing labeled (−)nicotine. IC 50 values for cholinergic drugs of (−)[ 3 H]nicotine binding were as follows: (−)‐nicotine, 0.51 n M ; acetylcholine, 12.6 n M ; (+)‐nicotine, 19.9 n M ; cytisine, 27.3 n M ; and carbachol, 527 n M. IC 50 values of α‐bungarotoxin, hexamethonium, d ‐tubocurarine, and atropine were larger than 50 μ M. (−)‐[ 3 H]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. These results suggest that nicotinic cholinergic receptors are present in human brain and that there are regional differences in the density of these receptors.