Thibaut F, Hirsch E C, Raisman R, Javoy-Agid F, Agid Y
INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Neuroscience. 1990;37(2):387-98. doi: 10.1016/0306-4522(90)90409-w.
The autoradiographic distribution of D1 dopaminergic binding sites was studied in the human ventral mesencephalon using the D1 antagonist [3H]SCH 23390. [3H]SCH 23390 binding was characterized by a single class of sites with a Kd of 2.5 nM and a Bmax of 31 fmol/mg of tissue. The density of [3H]SCH 23390 binding sites was high in the substantia nigra, moderate in the ventral tegmental area and low in the peri- and retrorubral field (catecholaminergic region A8). Binding densities were similar in pars compacta and pars reticulata of the substantia nigra, except for a peak value of high [3H]SCH 23390 in the pars reticulata, at a level just ventral to a zone of hyperdensity of melanized dopaminergic neurons in the pars compacta. The anatomical organization of the human ventral mesencephalon was analysed on adjacent sections stained for acetylcholinesterase histochemistry and tyrosine hydroxylase, substance P, dynorphin B, somatostatin and methionine-enkephalin immunohistochemistry, respectively. The similarity in distribution of [3H]SCH 23390 binding sites and substance P or dynorphin B immunoreactivity suggests that D1 binding sites are mainly located on the striatonigral projections. In accordance with these results: (1) the density of [3H]SCH 23390 binding sites was reduced in the substantia nigra of a patient with Huntington's chorea, a disease associated with a degeneration of striatonigral neurons; (2) the density of [3H]SCH 23390 binding sites was unaffected in the substantia nigra of a patient with Parkinson's disease, a disorder characterized by a marked loss in nigral tyrosine hydroxylase-positive neurons. [3H]SCH 23390 binding sites showed a characteristic, heterogeneous distribution within the human ventral mesencephalon, confirming data obtained in other species. The preferential localization of D1 dopamine receptors on striatonigral projections in human brain suggests that pharmacological manipulation of these receptors modulates the activity of striatonigral pathways, thereby affecting the various outputs of the nigral complex.
使用D1拮抗剂[3H] SCH 23390研究了人腹侧中脑D1多巴胺能结合位点的放射自显影分布。[3H] SCH 23390结合的特征是单一类别的位点，其解离常数（Kd）为2.5 nM，最大结合容量（Bmax）为31 fmol/mg组织。[3H] SCH 23390结合位点的密度在黑质中较高，在腹侧被盖区中等，在周围和红核后区（儿茶酚胺能区域A8）较低。黑质致密部和网状部的结合密度相似，除了网状部中[3H] SCH 23390的峰值，其水平刚好在致密部中黑化多巴胺能神经元高密度区的腹侧。分别在相邻切片上对人腹侧中脑的解剖结构进行了分析，这些切片分别用乙酰胆碱酯酶组织化学以及酪氨酸羟化酶、P物质、强啡肽B、生长抑素和甲硫氨酸脑啡肽免疫组织化学染色。[3H] SCH 23390结合位点与P物质或强啡肽B免疫反应性分布的相似性表明，D1结合位点主要位于纹状体黑质投射上。根据这些结果：（1）亨廷顿舞蹈病患者黑质中[3H] SCH 23390结合位点的密度降低，亨廷顿舞蹈病是一种与纹状体黑质神经元变性相关的疾病；（2）帕金森病患者黑质中[3H] SCH 23390结合位点的密度未受影响，帕金森病是一种以黑质酪氨酸羟化酶阳性神经元明显丧失为特征的疾病。[3H] SCH 23390结合位点在人腹侧中脑内呈现出特征性的异质性分布，证实了在其他物种中获得的数据。人脑中D1多巴胺受体在纹状体黑质投射上优先定位，这表明对这些受体的药理操作可调节纹状体黑质通路的活性，从而影响黑质复合体的各种输出。
