2ND-MESSENGER RESPONSES IN BRAIN-SLICES TO ELUCIDATE NOVEL GLUTAMATE RECEPTORS

G-Protein-coupled or 'metabotropic' glutamate receptors (mGluRs) are a novel heterogenous family of excitatory amino acid receptors. Activat ion of mGluRs in the rat hippocampus by the mcluR-selective agonist 1S ,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) leads to mu ltiple changes in second-messenger formation. These include increases in basal phosphoinositide hydrolysis, decreases in forskolin-stimulate d cAMP formation, and enhancement of cAMP formation via a potentiation of the effects of endogenous adenosine. These changes in mGluR coupli ng to phosphoinositide hydrolysis and the formation of cAMP likely ref lect the in situ expression of heterogenous populations of mGluRs. A n umber of electrophysiological studies on the functions of mGluRs in hi ppocampal circuitry, ontogeny, and cellular functions have also been d escribed. Any or all of these mGluR-mediated changes in second messeng ers may underlie the reported cellular effects associated with the mGl uR activation by 1S,3R-ACPD. However, mGluR agonists that have selecti vity for different mGluR second-messenger pathways are needed to sort out the cellular consequences of activating in situ expressed mGluR su btypes linked to specific second-messenger pathways.