Richfield E K, Penney J B, Young A B
Unit of Functional Neuroanatomy, National Institute of Mental Health, Bethesda, MD 20892.
Neuroscience. 1989;30(3):767-77. doi: 10.1016/0306-4522(89)90168-1.
The anatomical distributions and affinity states of dopamine D1 and D2 receptors were compared in the rat central nervous system using quantitative autoradiography. [3H]SCH23390 and [3H]spiperone (in the presence of 100 nM mianserin) were used to label the D1 and D2 receptors, respectively. The densities of D1 and D2 receptors displayed a positive correlation among 21 brain regions (Pearson correlation coefficient, r = 0.80, P less than 0.001). The affinity states for the D1 and D2 receptors were found to be quite different from each other, and different from the results obtained by others using homogenate preparations. Both the D1 and D2 receptors were best modeled using a two-state model. In the absence of exogenous guanine nucleotides and using the nonselective agonist dopamine as the competitor, the D1 receptor was primarily in a low affinity agonist state (RH = 21 +/- 6%), whereas the D2 receptor was primarily in the high affinity agonist state (RH = 77 +/- 3%). In the presence of 10 microM guanylyl-imidodiphosphate or guanosine-5'-O-(2-thiophosphate) both the D1 and the D2 receptor were completely in a low affinity agonist state (RL = 100%). These affinity states were found both in the nucleus accumbens and olfactory tubercle using dopamine as the competitor and in the striatum using selective D1 or D2 agonists as competitors. Receptor occupancy of the D2 receptor with either an agonist or antagonist did not alter the affinity states of the D1 receptor, and conversely, receptor occupancy of the D1 receptor did not alter the affinity states of the D2 receptor. The correlation between densities of D1 and D2 receptors provides an anatomical framework for evaluating behavioral and electrophysiological evidence of an interaction between the two dopamine receptor subtypes. This interaction does not appear to be due to a sharing or coupling of G-proteins in such a way that binding to one dopamine receptor subtype alters the affinity state of the other receptor subtype. The differences between dopamine receptor distributions described by labeled agonists and antagonists may be due in part to differences in their affinity states. The low proportion of high affinity state D1 receptors may explain some of the difficulties in assigning specific behavioral roles to the D1 receptor.
采用定量放射自显影术比较了大鼠中枢神经系统中多巴胺D1和D2受体的解剖分布及亲和力状态。分别使用[3H]SCH23390和[3H]螺哌隆（在100 nM米安色林存在的情况下）标记D1和D2受体。在21个脑区中，D1和D2受体的密度呈现正相关（Pearson相关系数，r = 0.80，P < 0.001）。发现D1和D2受体的亲和力状态彼此差异很大，且与其他人使用匀浆制剂获得的结果不同。D1和D2受体均最好用双态模型进行模拟。在不存在外源性鸟嘌呤核苷酸且使用非选择性激动剂多巴胺作为竞争者的情况下，D1受体主要处于低亲和力激动剂状态（RH = 21 ± 6%），而D2受体主要处于高亲和力激动剂状态（RH = 77 ± 3%）。在存在10 μM鸟苷酰亚胺二磷酸或鸟苷-5'-O-(2-硫代磷酸)的情况下，D1和D2受体均完全处于低亲和力激动剂状态（RL = 100%）。使用多巴胺作为竞争者时，在伏隔核和嗅结节中发现了这些亲和力状态，使用选择性D1或D2激动剂作为竞争者时，在纹状体中也发现了这些状态。D2受体被激动剂或拮抗剂占据均不会改变D1受体的亲和力状态，反之，D1受体被占据也不会改变D2受体的亲和力状态。D1和D2受体密度之间的相关性为评估这两种多巴胺受体亚型之间相互作用的行为和电生理证据提供了一个解剖学框架。这种相互作用似乎并非由于G蛋白的共享或偶联，使得与一种多巴胺受体亚型的结合改变了另一种受体亚型的亲和力状态。标记的激动剂和拮抗剂所描述的多巴胺受体分布之间的差异可能部分归因于它们亲和力状态的不同。高亲和力状态的D1受体比例较低可能解释了在赋予D1受体特定行为作用方面存在的一些困难。
