De Keyser J, De Backer J P, Vauquelin G, Ebinger G
Department of Neurology, Academisch Ziekenhuis, Vrije Universiteit, Brussels, Belgium.
J Neurochem. 1991 Apr;56(4):1130-3. doi: 10.1111/j.1471-4159.1991.tb11402.x.
D1 and D2 receptor densities in human substantia nigra were examined by use of the specific binding of, respectively, [3H]SCH 23390 [R(+)-7-chloro-8-hydroxy-3-[3H]methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine] and [3H]spiperone. A unilateral loss of striato- and pallidonigral pathways by an infarction (n = 4) had no effect on the ipsilateral nigral D2 receptors, but reduced the ipsilateral nigral D1 receptors by 48-60% compared with the intact side. These data suggest that a substantial fraction of D1 receptors in human substantia nigra is located on terminals of striato- and/or pallidonigral neurons, whereas D2 receptors are confined to intrinsic nigral cells. We also examined the effect of aging on the D1 and D2 receptors in substantia nigra obtained from 25 postmortem human brains (age range 19-88 years). The densities of both receptor types were not affected by the aging process. Since nigrostriatal dopaminergic neurons degenerate with aging, these results suggest either that the nigral D2 receptors are up-regulated in response to a progressive depletion of dopamine in the substantia nigra or that, in contrast to the rat, they are not located on dopaminergic neurons.
分别使用[3H]SCH 23390[R(+)-7-氯-8-羟基-3-[3H]甲基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓]和[3H]螺哌隆的特异性结合,检测了人黑质中D1和D2受体的密度。梗死导致单侧纹状体-黑质和苍白球-黑质通路缺失(n = 4)对同侧黑质D2受体无影响,但与完整侧相比,同侧黑质D1受体减少了48% - 60%。这些数据表明,人黑质中相当一部分D1受体位于纹状体-黑质和/或苍白球-黑质神经元的终末,而D2受体局限于黑质固有细胞。我们还研究了衰老对25例死后人类大脑(年龄范围19 - 88岁)黑质中D1和D2受体的影响。两种受体类型的密度均不受衰老过程的影响。由于黑质纹状体多巴胺能神经元随衰老而退化,这些结果表明,要么黑质D2受体因黑质中多巴胺的逐渐耗竭而发生上调,要么与大鼠不同,它们并不位于多巴胺能神经元上。