Catania M V, Landwehrmeyer G B, Testa C M, Standaert D G, Penney J B, Young A B
Department of Neurology, Massachusetts General Hospital Boston 02114.
Neuroscience. 1994 Aug;61(3):481-95. doi: 10.1016/0306-4522(94)90428-6.
The postnatal expression of metabotropic glutamate receptors was studied in rat brain by in situ hybridization and autoradiographic binding techniques. The messenger RNAs encoding five metabotropic glutamate receptor subtypes named mGluR1-5 had distinct regional and temporal expression profiles. mGluR1, mGluR2 and mGluR4 messenger RNA expression was low at birth and increased during postnatal development. In contrast, mGluR3 and mGluR5 were highly expressed at birth and decreased during maturation to adult levels of expression. [3H]Glutamate binding competition studies in developing brain disclosed the presence of two types of binding sites with the pharmacological properties of metabotropic glutamate receptors, having high (metabotropic type-1 binding sites; K1 = 8 nM) and low affinity (metabotropic type-2 binding sites; K1 = 50 microM) for quisqualic acid, as in adult rat brain. The densities of metabotropic binding sites changed during development in a complex, regionally specific fashion. Metabotropic type-1 binding sites were present at low levels at birth and gradually increased during the second postnatal week. In the striatum, globus pallidus and cerebellar granule layer, the increase in density of metabotropic type-1 binding sites was transient but persisted in the cerebellar molecular layer. In contrast, metabotropic type-2 binding sites were present at high densities in most regions in the first postnatal week and decreased during the second and third week, particularly in the thalamic reticular nucleus and globus pallidus. Only in the external cortex did both metabotropic type-1 and metabotropic type-2 binding sites increase during development. A striking correspondence between the temporal pattern of expression of specific metabotropic glutamate receptor transcripts and metabotropic binding sites was observed in the reticular nucleus of the thalamus (mGluR3; metabotropic type-2 binding sites) and cerebellum (mGluR1; metabotropic type-1 binding sites) suggesting early translation of these metabotropic glutamate receptor messenger RNAs into receptor proteins. In other regions the relationship between messenger RNA expression and binding sites was less direct: comparison between expression of metabotropic glutamate receptor messenger RNA and binding sites suggests both a pre- and postsynaptic location of some receptor subtypes. These data imply a functional role of mGluR3 and mGluR5 during synaptogenesis and maintenance of adult synapses and of mGluR1, mGluR2 and mGluR4 in mature synaptic transmission.
通过原位杂交和放射自显影结合技术，研究了大鼠脑中代谢型谷氨酸受体的产后表达。编码名为mGluR1 - 5的五种代谢型谷氨酸受体亚型的信使核糖核酸具有不同的区域和时间表达谱。mGluR1、mGluR2和mGluR4信使核糖核酸在出生时表达较低，在产后发育过程中增加。相反，mGluR3和mGluR5在出生时高表达，在成熟至成年表达水平的过程中下降。对发育中的大脑进行的[3H]谷氨酸结合竞争研究表明，存在两种具有代谢型谷氨酸受体药理学特性的结合位点，对喹啉酸具有高亲和力（代谢型1型结合位点；K1 = 8 nM）和低亲和力（代谢型2型结合位点；K1 = 50 μM），与成年大鼠脑相同。代谢型结合位点的密度在发育过程中以复杂的、区域特异性的方式变化。代谢型1型结合位点在出生时水平较低，在出生后第二周逐渐增加。在纹状体、苍白球和小脑颗粒层，代谢型1型结合位点密度的增加是短暂的，但在小脑分子层持续存在。相反，代谢型2型结合位点在出生后第一周在大多数区域高密度存在，在第二和第三周下降，特别是在丘脑网状核和苍白球。只有在大脑皮层外部，代谢型1型和代谢型2型结合位点在发育过程中都增加。在丘脑网状核（mGluR3；代谢型2型结合位点）和小脑（mGluR1；代谢型1型结合位点）中观察到特定代谢型谷氨酸受体转录本的表达时间模式与代谢型结合位点之间存在惊人的对应关系，这表明这些代谢型谷氨酸受体信使核糖核酸早期翻译成受体蛋白。在其他区域，信使核糖核酸表达与结合位点之间的关系不太直接：代谢型谷氨酸受体信使核糖核酸表达与结合位点之间的比较表明，一些受体亚型在突触前和突触后均有定位。这些数据表明mGluR3和mGluR5在突触形成和成年突触维持过程中发挥功能作用，而mGluR1、mGluR2和mGluR4在成熟突触传递中发挥作用。
