ANATOMICAL AND AFFINITY STATE COMPARISONS BETWEEN DOPAMINE-D1 AND DOPAMINE-D2 RECEPTORS IN THE RAT CENTRAL NERVOUS-SYSTEM
ANATOMICAL AND AFFINITY STATE COMPARISONS BETWEEN DOPAMINE-D1 AND DOPAMINE-D2 RECEPTORS IN THE RAT CENTRAL NERVOUS-SYSTEM
复制标题
DOI：
10.1016/0306-4522(89)90168-1
复制
发表时间：
1989-01-01
期刊：
影响因子：
3.3
通讯作者：
YOUNG, AB
中科院分区：
文献类型：
--
作者：
RICHFIELD, EK;PENNEY, JB;YOUNG, AB
采用定量放射自显影技术[3H]SCH23390比较多巴胺D1和D2受体在大鼠中枢神经系统中的解剖分布和亲和状态，分别用[3H]spiperone（在100 nM miaserin存在下）标记D1和D2受体。21个脑区D1和D2受体密度呈正相关（Pearson相关系数r = 0.80, P < 0.001）。对D1和D2受体的亲和力状态发现彼此有很大的不同，并且与其他人使用匀浆制备的结果不同。D1和D2受体都是最好的双态模型。在缺乏外源鸟嘌呤核苷酸和使用非选择性激动剂多巴胺作为竞争对手的情况下，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%)。当着10亩的面。鸟苷-5′- o -（2-硫代磷酸）D1和D2受体完全处于低亲和力激动剂状态（RL = 100%）。在以多巴胺为竞争对手的伏隔核和嗅结节以及以选择性D1或D2激动剂为竞争对手的纹状体中均发现了这种亲和性状态。D2受体与激动剂或拮抗剂的受体占用都不会改变D1受体的亲和力状态，相反，D1受体的受体占用也不会改变D1受体的亲和力状态。D1和D2受体密度之间的相关性为评估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解剖学框架。这种相互作用似乎不是由于g蛋白的共享或偶联，而g蛋白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。标记激动剂和拮抗剂描述的多巴胺受体分布的差异可能部分是由于它们的亲和状态的差异。高亲和状态D1受体的低比例可能解释了D1受体在分配特定行为作用方面的一些困难。
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 miaserin) 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 < 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 .mu.M 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 D1 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.