The mGluR proteins (metabotropic Glutamate Receptors) are members of the G-protein-coupled receptor family and are functionally and pharmacologically distinct from the GluR proteins (ionotropic Glutamate Receptors). The eight currently known mGluR proteins are mediated by two G-proteins with opposing regulation of adenylate cyclase pathways. The activities of mGluR1 and mGluR5 are mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. The remainder of the eight sub-types of mGluR have an activity mediated by a G-protein that inhibits adenylate cyclase activity. mGluR-3, which may interact with GRASP, acts as a receptor for glutamate.