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Complementary DNAs (cDNAs) encoding the human metabotropic glutamate receptor 4 (mGluR4) and human metabotropic glutamate receptor 7 (mGluR7) were isolated from a human cerebellum or fetal brain cDNA library by hybridization with probes that were generated by PCR and degenerate primers derived from rat mGluR sequences. The human mGluR4 and mGluR7 receptors are proteins of 912 and 915 amino acid residues long containing seven transmembrane spanning domains. They share 69% amino acid homology with each other. The human mGluR4 receptor has amino acid identity of 99.5% with rat mGluR7. The receptor cDNAs were subsequently cloned into a mammalian expression vector (pGT-h) which contains a major late promoter of Adenovirus Type 2. A RGT cell line [AV12-664 cells which have been stably transfected with a glutamate transporter (GLAST) to prevent the accumulation of glutamate into the medial stably transfected with these vectors was used to study selective inhibition of forskolin-stimulated cyclic AMP formation by mGluR agonists or antagonists. The data suggest that stimulation of mGluR4 and mGluR7 receptors with L-2 amino-4 amino-4 Phosphhonobutyrate (L-AP4) inhibited cAMP formation by 94% and 75% respectively.