Second-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. Activation of mGluRs in the rat hippocampus by the mGluR-selective agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) leads to multiple changes in second-messenger formation. These include increases in basal phosphoinositide hydrolysis, decreases in forskolin-stimulated cAMP formation, and enhancement of cAMP formation via a potentiation of the effects of endogenous adenosine. These changes in mGluR coupling to phosphoinositide hydrolysis and the formation of cAMP likely reflect the in situ expression of heterogenous populations of mGluRs. A number of electrophysiological studies on the functions of mGluRs in hippocampal circuitry, ontogeny, and cellular functions have also been described. Any or all of these mGluR-mediated changes in second messengers may underlie the reported cellular effects associated with the mGluR activation by 1S,3R-ACPD. However, mGluR agonists that have selectivity for different mGluR second-messenger pathways are needed to sort out the cellular consequences of activating in situ expressed mGluR subtypes linked to specific second-messenger pathways.