MOLECULAR CHARACTERIZATION OF A NOVEL RETINAL METABOTROPIC GLUTAMATE RECEPTOR MGLUR6 WITH A HIGH AGONIST SELECTIVITY FOR L-2-AMINO-4-PHOSPHONOBUTYRATE

A cDNA clone for a new metabotropic glutamate receptor, termed mGluR6, was isolated from a rat retinal cDNA library by cross-hybridization w ith the previously isolated cDNA clone for a metabotropic glutamate re ceptor. The cloned mGluR6 subtype consists of 871 amino acid residues and exhibits a structural architecture common to the metabotropic rece ptor family, possessing a large extracellular domain preceding the sev en putative membrane-spanning domains. mGluR6 shows the highest sequen ce similarity to mGluR4 among the metabotropic receptor subtypes and i nhibits the forskolin-stimulated cyclic AMP accumulation in Chinese ha mster ovary cells transfected with the cloned cDNA. mGluR6 potently re acts with L-2-amino-4-phosphonobutyrate (L-AP4) and L-serine-O-phospha te, and the potencies of these compounds are one order of magnitude gr eater than that of L-glutamate. Blot and in situ hybridization analyse s indicated that mGluR6 mRNA is restrictedly expressed in the inner nu clear layer of the retina where ON-bipolar cells are distributed. The metabotropic receptor that responds strongly to L-AP4 and L-serine-O-p hosphate in ON-bipolar cells is known to mediate glutamate synaptic tr ansmission between photoreceptor cells and ON-bipolar cells. On the ba sis of the agonist selectivity of mGluR6 and its specific expression i n retinal cells, the physiological role of this receptor subtype in th e visual system is discussed.