Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4

作者：Yasuto Tanabe, Akihiro Nomura, Masayuki Masu, Ryuichi Shigemoto, Noboru Mizuno, Shigetada Nakanishi · 发表于：Journal of Neuroscience · 年份：1993 · DOI：10.1523/jneurosci.13-04-01372.1993 · 被引用次数：579 · 研究领域：Neuroscience and Neuropharmacology Research、Photochromic and Fluorescence Chemistry、Medicinal Plants and Neuroprotection

The metabotropic glutamate receptors are coupled to intracellular signal transduction via G-proteins and consist of a family of at least five different subtypes, termed mGluR1-mGluR5. We studied the signal transduction mechanism and pharmacological characteristics of the rat mGluR3 and mGluR4 subtypes in Chinese hamster ovary cells permanently expressing the cloned receptors. Both mGluR3 and mGluR4 inhibit the forskolin-stimulated accumulation of intracellular cAMP formation in response to agonist interaction. Consistent with the high degree of sequence similarity to mGluR2, mGluR3 closely resembles mGluR2 in its agonist selectivity; the potency rank order of agonists is L-glutamate > trans-1-aminocyclopentane-1,3-dicarboxylate > ibotenate > quisqualate. mGluR4 is totally different in its agonist specificity from any other member of the metabotropic receptors. This receptor potently reacts with L-2-amino-4-phosphonobutyrate (L-AP4) in a stereo-selective manner and moderately responds to L-serine-O-phosphate. mGluR4 thus corresponds well to the putative L-AP4 receptor characterized from brain preparations. Blot and in situ hybridization analyses indicated that both mRNAs are widely distributed in the rat brain. mGluR3 mRNA is highly expressed in neuronal cells of the cerebral cortex and the caudate-putamen, and in granule cells of the hippocampal dentate gyrus. The expression pattern of mGluR4 mRNA is more restricted, and this expression is prominent in the cerebellum, olfacto...