Regional distribution of subtypes of nicotinic receptors in human brain and effect of aging studied by (±)-[3H]epibatidine

Epibatidine, a potent nicotinic agonist, was used to study the regional distribution of nicotinic acetylcholine receptor binding sites in the human brain. Saturation studies performed in the human temporal cortex with (+/-)-[H-3]epibatidine revealed binding to two binding sites with K-d and B-max values of 0.018 and 4.2 nM, 12.7 and 15.4 fmol/mg protein, respectively. Competition studies with (+/-)-[H-3]epibatidine/unlahelled nicotine or [H-3]nicotine/unlabelled (+/-)-epibatidine showed binding to two binding sites in the human temporal cortex (K-i = 0.16 and 12.6 nM; 0.007 and 0.3 nM, respectively). Similarly, when unlabelled nicotine was used to displace (+/-)-[H-3]epibatidine, two binding sites were also revealed in the thalamus and the cerebellum of human brain (K-i = 0.065 and 7.7 nM; 0.07 and 12.5 nM, respectively). The regional binding of(+/-)-[H-3]epibatidine binding in human brain was somewhat different from that of [H-3]nicotine. A proportionally higher binding was observed for(+/-)-[H-3]epibatidine in the cerebellum and the thalamus compared to [H-3]nicotine, probably reflecting different selectivity to nicotinic receptor subtypes. A marked significant age-related decrease in (+/-)-[H-3]epibatidine binding was observed in the frontal and the temporal cortices (-79%, - 84%, respectively) of human subjects between 56-85 years of age, which was similar to that of [H-3]nicotine (- 82%, - 79%, respectively). The (+/-)-[H-3]epibatidine binding in the cerebellum decreased significantly with age (-77%), while [H-3]nicotine binding showed no significant age-related changes in this brain region. The findings indicate that a specifically modulate regional nicotinic receptors in human brain. (C) 1998 Elsevier Science B.V. All rights reserved.