CLONING AND EXPRESSION OF A NEW MEMBER OF THE L-2-AMINO-4-PHOSPHONOBUTYRIC ACID-SENSITIVE CLASS OF METABOTROPIC GLUTAMATE RECEPTORS

Despite the cloning of several metabotropic glutamate receptors (MGluR 1-6), the activity and localization of the cloned mGluRs do not accoun t for the action of L-2-amino-4-phosphonobutyric acid (L-AP4) on mitra l/tufted cells in the rat olfactory bulb. Thus, we screened a rat olfa ctory bulb library for novel cDNA clones, using probes derived from mG luR1 and mGluR4. A full length cDNA clone encoding a metabotropic rece ptor (mGluR7) whose sequence was 69% identical to that of mGluR4 was i solated. Stimulation of mGluR7 with L-AP4 and glutamate (each at 1 mm) in stably transfected baby hamster kidney cells inhibited forskolin-s timulated cAMP formation, whereas ACPD (1 mM) and quisqualate (0.5 mM) were less effective. Inhibition of cAMP required high concentrations of agonist in the transfected cells, suggesting that inhibition of ade nylate cyclase may not be the predominant transduction mechanism for t his receptor in neurons. RNA blot analysis and in situ hybridization r evealed that mGluR7 has an expression pattern in the central nervous s ystem distinct from that of other L-AP4-sensitive mGluRs. Double-label ing with probes for mGluR1 and mGluR7 revealed that individual mitral/ tufted neurons in the olfactory bulb expressed both mRNAs. The express ion pattern and L-AP4 sensitivity of mGluR7 suggest that it mediates i nhibition of transmitter release at selected glutamatergic synapses. T he coexpression of multiple mGluR mRNAs in single neurons indicates th at the cellular effects of mGluR activation are likely to result from the integrated action of several receptor subtypes.