Group I metabotropic glutamate receptors: Implications for brain diseases

Glutamate is the major excitatory neurotransmitter in the brain and plays a unique role in a variety of central nervous system (CNS) functions. The di scovery of the metabotropic receptors (mGluRs), a family of G-protein coupl ed receptors than can be activated by glutamate, has led to an impressive n umber of studies in recent years aimed at understanding their biochemical, physiological and pharmacological characteristics. The eight mGluRs now known are divided into three groups according to their sequence homology, signal transduction mechanisms, and agonist selectivity . Group I mGluRs include mGluR(1) and mGluR(5), which are linked to the act ivation of phospholipase C, Groups II and III include all others and are ne gatively coupled to adenylyl cyclases. Thr availability in recent years of agents selective for Group I mGluRs has made possible the study of the physiological roles of these receptors in t he CNS. In addition to mediating glutamatergic neurotransmission, Group I m GluRs can modulate other neurotransmitter receptors. including GABA and the ionotropic glutamate receptors. Group I mGluRs are involved in many CNS functions and may participate in a variety of disorders such as pain, epilepsy, ischemia, and chronic neurodeg enerative diseases. This class of receptor may provide important pharmacolo gical therapeutic targets and elucidating its functions will be relevant to develop new treatments for neurological and psychiatric disorders in which glutamatergic neurotransmission is abnormally regulated. In this review anatomical, physiological and pharmacological results are pr esented with a special emphasis on the role of Group I mGluRs in functional and pathological processes. (C) 1999 Elsevier Science ltd. All rights rese rved.