CLONING, DISTRIBUTION AND FUNCTIONAL EXPRESSION OF THE HUMAN MGLU(6) METABOTROPIC GLUTAMATE-RECEPTOR

The cDNA encoding the human metabotropic glutamate receptor type 6 (hm Glu(6)) was isolated from a human retinal cDNA library. The deduced pr imary sequence (877 amino acids) of the hmGlu(6) receptor was 93.5% id entical to its rat counterpart and shared 69.8% sequence identity with the related hmGlu(4) receptor clone (912 amino acids), isolated in pa rallel from a human brain cDNA library. In situ hybridization revealed that the hmGlu(6) mRNA is highly expressed in cells located in the in ner nuclear layer of the human retina, presumably bipolar neurons. Nei ther PCR analysis nor in situ hybridization could detect hmGlu(6) mRNA in human brain. When stably expressed in Chinese hamster ovary cells (CHO-K1) the hmGlu(6) receptor inhibited adenylate cyclase through a p ertussis toxin-sensitive G-protein, and reduced forskolin-elevated cyc lic adenosine monophosphate (cAMP) levels in response to agonists. The rank order of agonist potency was L(+)-2-amino-4-phosphonobutyric aci d (L-AP4) > L-serine-O-phosphate > L-glutamate > quisqualate = (1S,3R) -1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD). (2S,3S,4S)- alpha-(carboxycyclopropyl)-glycine (L-CCG-I) was a partial agonist at the hmGlu(6) receptor, with a potency approaching that of L-serine-O-p hosphate. (C) 1997 Published by Elsevier Science Ltd.