Broussolle E P, Wong D F, Fanelli R J, London E D
Addition Research Center, National Institute on Drug Abuse, Baltimore, MD 21224.
Life Sci. 1989;44(16):1123-32. doi: 10.1016/0024-3205(89)90340-8.
[3H] 1-Nicotine was used as a receptor ligand in the intact mouse. It was injected i.v., and radioactivity in brain regions was assayed. Nonspecific binding was estimated by pretreatment with unlabelled 1-nicotine. Radioactivity entered the brain rapidly, was heterogeneously distributed, and declined after 5 min. Estimated specific binding was highest in the medial and posterior cortex, midbrain, thalamus/hypothalamus and medulla/pons; intermediate in the cerebellum, caudate/putamen, frontal and frontoparietal cortex; and lowest in the hippocampus and olfactory bulb. Autoradiography showed similar patterns. Coinjection of unlabelled 1-nicotine reduced specific binding so that it approached estimated nonspecific binding. Nicotinic agonists reduced radioactivity in the thalamus/hypothalamus, but nicotinic antagonists were less active. Non-nicotinic drugs did not reduce brain radioactivity. The results suggest that radiolabelled nicotine may be used for in vivo receptor studies despite problems in estimating nonspecific binding.
[3H]1-尼古丁在完整小鼠中用作受体配体。通过静脉注射给予，然后测定脑区的放射性。用未标记的1-尼古丁预处理来估计非特异性结合。放射性迅速进入大脑，分布不均匀，并在5分钟后下降。估计的特异性结合在内侧和后皮质、中脑、丘脑/下丘脑和延髓/脑桥中最高；在小脑、尾状核/壳核、额叶和额顶叶皮质中居中；在海马体和嗅球中最低。放射自显影显示出类似的模式。共同注射未标记的1-尼古丁会降低特异性结合，使其接近估计的非特异性结合。烟碱激动剂会降低丘脑/下丘脑的放射性，但烟碱拮抗剂的活性较低。非烟碱类药物不会降低脑放射性。结果表明，尽管在估计非特异性结合方面存在问题，但放射性标记的尼古丁可用于体内受体研究。
