Boyson S J, McGonigle P, Molinoff P B
J Neurosci. 1986 Nov;6(11):3177-88. doi: 10.1523/JNEUROSCI.06-11-03177.1986.
The distribution of D1 and D2 receptors was studied in coronal sections of rat brain, using quantitative autoradiography. D1 receptors were labeled with 1.8 nM 3H-SKF-83566 (a brominated analog of 3H-SCH-23390), while D2 receptors were labeled with 1.0 nM 3H-spiroperidol (3H-SPD). The binding of both ligands to sections from brain and from a homogenate of caudate putamen (CPu mash) reached equilibrium within 80 min at 37 degrees C. CPu mash provided a virtually unlimited number of homogeneous sections that contained a high density of both D1 and D2 receptors. Sections of CPu mash were used in competition studies that confirmed that the specific binding of 3H-SKF-83566 was selective for D1 receptors, and that the binding of 3H-SPD was selective for D2 receptors. Scatchard analysis of equilibrium binding of the 2 ligands in the CPu in horizontal sections of rat brain revealed Kd values of 1.1 +/- 0.07 nM for 3H-SKF-83566 and 0.7 +/- 0.09 nM for 3H-SPD. Studies of the distribution of D1 and D2 receptors were carried out in coronal sections of brains from 5 rats. D1 receptors were found throughout the forebrain and were present in greater density than were D2 receptors in all regions examined except the olfactory nerve layer. In the CPu, nucleus accumbens, and olfactory tubercle, the densities of D1 and D2 receptors were, respectively, approximately 2,500 and 600-800 fmol/mg protein. In the substantia nigra, the density of D1 receptors was approximately 2,500 fmol/mg protein in both the compacta and the reticulata, but the density of D2 receptors was 230 fmol/mg protein in the compacta and 70 fmol/mg protein in the reticulata. The ventral tegmental area contained only 90 fmol/mg protein of D1 receptors, and D2 receptors were undetectable. The entopeduncular nucleus, zona incerta, and region of the ventral internal capsule had densities of D1 receptors of 550-950 fmol/mg protein and D2 receptor densities of less than 100 fmol/mg protein. Densities of D1 and D2 receptors were, respectively, 2,700 and 900 fmol/mg protein in the choroid plexus. Knowledge of the differences in the relative distributions of D1 and D2 receptors in various brain regions may increase our understanding of the functions of brain dopaminergic systems and may aid in the development of new therapeutic approaches for neuropsychiatric disorders.
采用定量放射自显影术，研究大鼠脑冠状切片中D1和D2受体的分布。用1.8 nM 3H-SKF-83566（3H-SCH-23390的溴化类似物）标记D1受体，而用1.0 nM 3H-螺哌啶醇（3H-SPD）标记D2受体。两种配体与脑切片和尾状壳核匀浆（CPu匀浆）的结合在37℃下80分钟内达到平衡。CPu匀浆提供了数量几乎无限的均匀切片，其中含有高密度的D1和D2受体。CPu匀浆切片用于竞争研究，证实3H-SKF-83566的特异性结合对D1受体具有选择性，而3H-SPD的结合对D2受体具有选择性。对大鼠脑水平切片中CPu内两种配体的平衡结合进行Scatchard分析，结果显示3H-SKF-83566的Kd值为1.1±0.07 nM，3H-SPD的Kd值为0.7±0.09 nM。对5只大鼠脑的冠状切片进行了D1和D2受体分布的研究。D1受体在前脑各处均有发现，除嗅神经层外，在所检查的所有区域中，其密度均高于D2受体。在CPu、伏隔核和嗅结节中，D1和D2受体的密度分别约为2500和600 - 800 fmol/mg蛋白。在黑质中，致密部和网状部D1受体的密度均约为2500 fmol/mg蛋白，但致密部D2受体密度为230 fmol/mg蛋白，网状部为70 fmol/mg蛋白。腹侧被盖区仅含90 fmol/mg蛋白的D1受体，未检测到D2受体。内苍白球核、未定带和腹侧内囊区域的D1受体密度为550 - 950 fmol/mg蛋白，D2受体密度小于100 fmol/mg蛋白。脉络丛中D1和D2受体的密度分别为2700和900 fmol/mg蛋白。了解不同脑区D1和D2受体相对分布的差异，可能会增进我们对脑多巴胺能系统功能的理解，并有助于开发针对神经精神疾病的新治疗方法。
