Shimohama S, Taniguchi T, Fujiwara M, Kameyama M
J Neurochem. 1985 Aug;45(2):604-10. doi: 10.1111/j.1471-4159.1985.tb04029.x.
(-)-[3H]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 (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, nicotinic agonists were 1,000 times more potent than ganglionic, neuromuscular, and muscarinic blocking drugs in displacing labeled (-)-nicotine. IC50 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 larger than 50 microM. (-)-[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. These results suggest that nicotinic cholinergic receptors are present in human brain and that there are regional differences in the density of these receptors.
尸检获得的人脑膜被发现能特异性结合（-）-[³H]尼古丁。这种结合具有立体特异性，（-）-尼古丁在取代标记的（-）-尼古丁方面的效力比（+）-尼古丁高40倍。饱和结合研究显示存在两个结合位点，解离常数（KD）值分别为8.1和86 nM，最大结合容量（Bmax）值分别为36和90 fmol/mg蛋白质。在竞争研究中，烟碱激动剂在取代标记的（-）-尼古丁方面比神经节、神经肌肉和毒蕈碱阻断药物的效力高1000倍。（-）-[³H]尼古丁结合的胆碱能药物的IC50值如下：（-）-尼古丁，0.51 nM；乙酰胆碱，12.6 nM；（+）-尼古丁，19.9 nM；金雀花碱，27.3 nM；卡巴胆碱，527 nM。α-银环蛇毒素、六甲铵、d-筒箭毒碱和阿托品的IC50值大于50 μM。在所测试的脑区中，（-）-[³H]尼古丁结合在迈内特基底核和丘脑中最高，在大脑皮层和尾状核中最低。这些结果表明人脑存在烟碱胆碱能受体，且这些受体的密度存在区域差异。
