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一种在视网膜和嗅球中表达的新型代谢型谷氨酸受体。

A novel metabotropic glutamate receptor expressed in the retina and olfactory bulb.

作者信息

Duvoisin R M, Zhang C, Ramonell K

机构信息

Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Cornell University Medical College, New York, New York 10021, USA.

出版信息

J Neurosci. 1995 Apr;15(4):3075-83. doi: 10.1523/JNEUROSCI.15-04-03075.1995.

Abstract

A novel metabotropic glutamate receptor, mGluR8, was identified by screening a mouse retina cDNA library. This receptor is most related to mGluR4, mGluR7, and mGluR6 (74%, 74%, and 70% identical amino acid residues, respectively). Similar to these receptors, stimulation by L-glutamate or L-2-amino-4-phosphonobutyrate (L-APB) of Chinese hamster ovary (CHO) cells stably transfected with mGluR8 result in the inhibition of forskolin-stimulated adenylyl cyclase. In situ hybridization studies revealed a strong expression of the mGluR8 gene in the olfactory bulb, accessory olfactory bulb, and mammillary body. A weaker expression was found in the retina, and in scattered cells in the cortex and hindbrain. During development, the distribution of mGluR8 expression was more widespread. These results extend the diversity of metabotropic glutamate receptors in the CNS. Because at least two APB receptors are expressed in the retina, the use of this drug to block selectively the ON pathway needs to be reconsidered. The pharmacology and expression of mGluR8 in mitral/tufted cells suggest it could be a presynaptic receptor modulating glutamate release by these cells at their axon terminals in the entorhinal cortex.

摘要

通过筛选小鼠视网膜cDNA文库,鉴定出一种新型代谢型谷氨酸受体mGluR8。该受体与mGluR4、mGluR7和mGluR6关系最为密切(氨基酸残基的同源性分别为74%、74%和70%)。与这些受体相似,用L-谷氨酸或L-2-氨基-4-膦酸丁酸(L-APB)刺激稳定转染mGluR8的中国仓鼠卵巢(CHO)细胞,会导致福斯可林刺激的腺苷酸环化酶受到抑制。原位杂交研究显示,mGluR8基因在嗅球、副嗅球和乳头体中强烈表达。在视网膜以及皮质和后脑的散在细胞中发现较弱的表达。在发育过程中,mGluR8表达的分布更为广泛。这些结果扩展了中枢神经系统中代谢型谷氨酸受体的多样性。由于视网膜中至少表达两种APB受体,因此需要重新考虑使用这种药物来选择性阻断ON通路。mGluR8在二尖瓣/簇状细胞中的药理学和表达表明,它可能是一种突触前受体,在这些细胞的轴突终末调节内嗅皮质中谷氨酸的释放。

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