ABSTRACT
Ion channel linked (ionotropic) glutamate receptors were recognized decades ago to play a direct role in fast excitatory synaptic transmission within the majority of synapses of the central nervous system (see Watkins and Evans, 1981; Watkins, 1986). More recently, “metabotropic” glutamate (mGlu) receptors are recognized as a novel heterogeneous family of G-protein coupled receptor proteins which function to modulate glutamate transmission via pre-synaptic, post-synaptic, and glial mechanisms (see Pin and Duvoisin, 1995; Conn and Pin, 1997; Anwyl, 1999). Currently, eight subtypes of mGlu receptors (mGlu1-8) have been cloned; their structure and function have been described in the preceding chapter (Pin and Bockaert, 1999). Briefly, group I mGlu receptors are coupled to activation of phospholipase C and include mGlu1 and mGlu5 (and their slice variants). Both group II mGlu receptors (mGlu2 and mGlu3) and group III (mGlu4, mGlu6, mGlu7, and mGlu8) are coupled via Gi to inhibition of adenylate cyclase. The basis for describing mGlu receptors into these three groups was originally described by Nakanishi (1992) and included (1) structural homology of about 70 percent within groups and about 40 percent between groups, (2) similar transduction mechanisms or G-protein coupling, and (3) shared pharmacological properties within a group. This classification of mGlu receptors into groups has been very useful for describing the pharmacological actions of many novel agents. Many current agents are selective for mGlu receptor groups but they do not distinguish between subtypes within a group. Thus, this classification has been very useful for understanding the relative role of each mGlu receptor group in modulation of excitatory synaptic transmission. However, better pharmacological tools are needed to distinguish clearly the relative role of a single mGlu receptor subtype. The recent development of agents with subtype selectivity within an mGlu receptor group will be very useful. Also, a clearer understanding of the actions of known agents across all eight known receptors is needed. With this in mind, we have recently reviewed the literature in detail on the effects of known pharmacological agents across all eight mGlu receptor subtypes (Schoepp et al., 1999a).
