Friberg I K, Young A B, Standaert D G
Neurology Service, Massachusetts General Hospital and Harvard Medical School, Fruit Street, Boston, MA 02114, USA.
Brain Res Mol Brain Res. 1998 Mar 1;54(2):298-310. doi: 10.1016/s0169-328x(97)00346-x.
The corticostriatal pathway is among the largest glutamatergic pathways in the brain, and of particular interest to the study of glutamatergic transmission. The metabotropic glutamate receptors (mGluRs) couple the actions of glutamate to intracellular second messenger systems through G-proteins. The most prominent of the mGluRs present in the target of this pathway, the striatum, is mGluR5. The identity of the G-proteins mediating the actions of mGluR5 are unknown, but the receptor is linked to stimulation of phosphoinositide (PI) turnover and largely resistant to the effects of pertussis toxin, which inhibits some G-proteins. We used in situ hybridization to examine the expression and regulation of three pertussis toxin insensitive G-protein alpha sub-units: Gq, G11, and Gz. We found that these mRNAs are differentially distributed in the rat brain, but all three are expressed by striatal neurons. After glutamatergic deafferentation of the striatum by decortication, there is a modest upregulation of G11 mRNA, while expression of Gq and Gz are unchanged. Following dopaminergic deafferentation, expression of Gq, G11, and Gz are not altered, although expression of the pertussis-sensitive sub-unit Go is increased. Our data suggests that Gz, Gq, and G11 are each expressed by striatal neurons, and therefore may be involved in mediating the actions of mGluR5 in these cells. After decortication G11 is upregulated, but the magnitude of this effect is small, and alone seems insufficient to account for the marked biochemical supersensitivity of glutamate-stimulated PI turnover which is observed.
皮质纹状体通路是大脑中最大的谷氨酸能通路之一，对谷氨酸能传递的研究尤为重要。代谢型谷氨酸受体（mGluRs）通过G蛋白将谷氨酸的作用与细胞内第二信使系统偶联起来。在该通路的靶标纹状体中存在的最主要的mGluR是mGluR5。介导mGluR5作用的G蛋白的身份尚不清楚，但该受体与磷酸肌醇（PI）周转的刺激有关，并且在很大程度上对百日咳毒素的作用具有抗性，百日咳毒素会抑制一些G蛋白。我们使用原位杂交技术来检测三种对百日咳毒素不敏感的G蛋白α亚基：Gq、G11和Gz的表达及调控。我们发现这些mRNA在大鼠脑中分布不同，但这三种亚基均由纹状体神经元表达。通过去皮质术使纹状体谷氨酸能传入纤维脱失后，G11 mRNA有适度上调，而Gq和Gz的表达未改变。多巴胺能传入纤维脱失后，Gq、G11和Gz的表达未改变，尽管对百日咳敏感的亚基Go的表达增加。我们的数据表明，Gz、Gq和G11均由纹状体神经元表达，因此可能参与介导这些细胞中mGluR5的作用。去皮质术后G11上调，但这种效应的程度较小，单独来看似乎不足以解释所观察到的谷氨酸刺激的PI周转的明显生化超敏感性。
