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.
Marutle
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A
Department of Neuroscience and Family Medicine, Division of Molecular Neuropharmacology, Karolinska Institutet, Huddinge University Hospital, B 84 Huddinge S-141 86, Sweden. amelia.marutle@kfcmail.hs.sll.se
Warpman
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U
Bogdanovic
N
N
Nordberg
A
A
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007536:Isomerism; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000032:analysis / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000032:analysis / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000032:analysis*; D014316:Tritium
D019086:Bridged Bicyclo Compounds, Heterocyclic; D011725:Pyridines; D011978:Receptors, Nicotinic; D014316:Tritium; D009538:Nicotine; C082748:epibatidine