Pharmacology and physiology of metabotropic glutamate receptors in mammalian central nervous system

Abstract Until recently, all receptors for glutamate and other excitatory amino acids (EAAs) were thought to be ligand‐regulated cation channels which, when activated, lead directly to cell depolarization. This family of glutamate receptors is referred as the ionotropic glutamate receptor family and is involved in transmission of fast synaptic responses. It is now clear that glutamate also acts on a distinct family of metabotropic receptors. These glutamate receptors are not cation channels but are linked to effector systems via guanine nucleotide binding proteins (G‐proteins). To date, the best‐characterized G protein‐coupled glutamate receptor is linked to phospholipase C and stimulation of phosphoinositide hydrolysis. The pharmacology of this receptor subclass has been thoroughly investigated and is clearly distinct from that of the ionotropic glutamate receptors. Until recently, little was known about the physiological roles of the metabotropic glutamate receptors. However, the recent discovery of selective metabotropic glutamate receptor agonists has made it possible to begin to investigate the physiological effects of activation of this novel class of glutamate receptor.