Expression and signaling of group I metabotropic glutamate receptors in astrocytes and microglia

Stimulation of astrocytes with the excitatory neurotransmitter glutamate le ads to the formation of inositol 1,4,5-trisphosphate and the subsequent inc rease of intracellular calcium content. Astrocytes express both ionotropic receptors and metabotropic glutamate (mGlu) receptors, of which mGlu(5) rec eptors are probably involved in glutamate-induced calcium signaling. The mG lu(5) receptor occurs as two splice variants, mGlu,, and mGlu(5a), but it w as hitherto unknown which splice Variant is responsible for the glutamate-i nduced effects in astrocytes, We report here that both mRNAs encoding mGlu( 5) receptor splice variants are expressed by cultured astrocytes. The expre ssion of mGlu(5a) receptor mRNA is much stronger than that of mGlu(5b) rece ptor mRNA in these cells. In situ hybridization experiments reveal neuronal expression of mGlu(5a) receptor mRNA in adult rat forebrain but a strong n euronal expression of mGlu(5a) mRNA only in olfactory bulb. Signals for mGl u(5a) receptor mRNA in the rest of the brain were diffuse and weak but cons istently above background. Activation of mGlu(5) receptors in astrocytes yi elds increases in inositol phosphate production and transient calcium respo nses. It is surprising that the rank order of agonist potency [quisqualate > (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine = trans-(1S,3R)-1-amino-1,3-cy clopentanedicarboxylic acid (1S,3R-ACPD) > glutamate] differs from that rep orted for recombinantly expressed mGlu(5a) receptors, The expression of mGl u(5a) receptor mRNA and the occurrence of 1S,3R-ACPD-induced calcium signal ing were found also in cultured microglia, indicating for the first time ex pression of mGlu(5a) receptors in these macrophage-like cells.