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 (+/-)-[3H]epibatidine revealed binding to two binding sites with Kd and Bmax values of 0.018 and 4.2 nM, 12.7 and 15.4 fmol/mg protein, respectively. Competition studies with (+/-)-[3H]epibatidine/unlabelled nicotine or [3H]nicotine/unlabelled (+/-)-epibatidine showed binding to two binding sites in the human temporal cortex (Ki=0.16 and 12.6 nM; 0.007 and 0.3 nM, respectively). Similarly, when unlabelled nicotine was used to displace (+/-)-[3H]epibatidine, two binding sites were also revealed in the thalamus and the cerebellum of human brain (Ki=0.065 and 7.7 nM; 0.07 and 12.5 nM, respectively). The regional binding of (+/-)-[3H]epibatidine binding in human brain was somewhat different from that of [3H]nicotine. A proportionally higher binding was observed for (+/-)-[3H]epibatidine in the cerebellum and the thalamus compared to [3H]nicotine, probably reflecting different selectivity to nicotinic receptor subtypes. A marked significant age-related decrease in (+/-)-[3H]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 [3H]nicotine (-82%, -79%, respectively). The (+/-)-[3H]epibatidine binding in the cerebellum decreased significantly with age (-77%), while [3H]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.