Most central nervous system D2 dopamine receptors are coupled to their effecters by Go
Most central nervous system D2 dopamine receptors are coupled to their effecters by Go
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DOI：
10.1073/pnas.051632598
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发表时间：
2001-03-13
影响因子：
11.1
通讯作者：
Birnbaumer, L
中科院分区：
文献类型：
--
作者：
Jiang, MS;Spicher, K;Birnbaumer, L
我们以前报道过Go缺陷小鼠出现严重的神经系统缺陷，包括痛觉过敏、全身性震颤、缺乏协调和转向综合征，有点像多巴胺能黑质-纹状体通路的单侧病变。通过使用正常和Go缺陷小鼠连续切片的脑的冷冻冠状切片，我们研究了几种G蛋白偶联受体促进GTP γ S与G蛋白结合的能力以及CTP促进D2多巴胺受体对其生理激动剂多巴胺的亲和力转变的能力。我们发现了一个普遍的，但不是完全减少激动剂刺激结合GTP γ S冷冻脑切片，没有显着的左，右差异。出乎意料的是，GTP调节多巴胺与D2受体结合亲和力的能力（如在原位[S-35]舒必利置换曲线中所见）在对照小鼠中是稳健的，在Go缺陷小鼠中不存在。这些数据表明，在中枢神经系统中的Gi/Go偶联D2受体的大部分作用是由Go而不是Gi 1，Gi 2或Gi 3介导的。与此一致，GTP对双Gi 1 + Gi 2-和Gi 1 + Gi 3-缺陷小鼠中多巴胺与D2受体结合的影响基本上不受影响。
We reported previously that Go-deficient mice develop severe neurological defects that include hyperalgesia, a generalized tremor, lack of coordination, and a turning syndrome somewhat reminiscent of unilateral lesions of the dopaminergic nigro-striatal pathway. By using frozen coronal sections of serially sectioned brains of normal and Go-deficient mice, we studied the ability of several G protein coupled receptors to promote binding of GTP gammaS to G proteins and the ability of CTP to promote a shift in the affinity of D2 dopamine receptor for its physiologic agonist dopamine. We found a generalized, but not abolished reduction in agonist-stimulated binding of GTP gammaS to frozen brain sections, with no significant left-right differences. Unexpectedly, the ability of GTP to regulate the binding affinity of;dopamine to D2 receptors (as seen in in situ [S-35]sulpiride displacement curves) that was robust in control mice, was absent in Go-deficient mice. The data suggest that most of the effects of the Gi/Go-coupled D2 receptors in the central nervous system are mediated by Go instead of Gi1, Gi2, or Gi3. In agreement with this, the effect of GTP on dopamine binding to D2 receptors in double Gi1 plus Gi2- and Gi1 plus Gi3-deficient mice was essentially unaffected.