A NOVEL SPLICE VARIANT OF A METABOTROPIC GLUTAMATE-RECEPTOR, HUMAN MGLUR7B

Two splice variants of the human metabotropic glutamate receptor 7, na med hmGluR7a and hmGluR7b, were isolated from a human brain cDNA libra ry. The isoforms differ by an out-of-frame insertion of 92 nucleotides close to the C-terminus of the hmGluR7 coding region. hmGluR7a has a length of 915 amino acids and represents the human homolog of the rece ntly cloned rat mGluR7. hmGluR7b is seven amino acids longer and exhib its a novel C-terminus of 23 amino acids in length. RT-PCR analysis de monstrated the existence of mGluR7b transcripts in wild-type mouse bra in and its absence in mGluR7 knockout mice. Northern blot analyses ind icate that mGluR7 expression is developmentally regulated. It is expre ssed at high levels in human fetal brain and at a lower level in many regions of adult human brain. Stimulation of hmGluR7b with L-2-amino-4 -phosphonobutyrate (L-AP4), L-serine-O-phosphate (L-SOP) or L-glutamat e in stably transfected Chinese hamster ovary (CHO) cells depressed fo rskolin-induced cAMP accumulation, whereas (1S,3R)-1-aminocycloperdane -1,3-dicarboxylic acid ((1S,3R)-ACPD) and quisqualate (both at 1 mM) h ad no significant effects. As described for rat mGluR7, the rank order of agonist potencies is: L-SOP, L-AP4 > L-glutamate >(1S,3R)-ACPD, qu isqualate. (C) 1997 Elsevier Science Ltd.