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 mGluR-1 and mGluR-5 are mediated by a G protein that activates a phosphatidylinositolcalcium second messenger system and generates a calcium-activated chloride current. The remainder of the eight subtypes of mGluR have an activity mediated by a G protein that inhibits adenylate cyclase activity. mGluR-7, which can interact with PRKCABP, acts as a receptor for glutamate. It is highly expressed in various areas of the brain, but highest levels are detected in cerebellum, cerebral cortex and hippocampus.