Novel functions for subtypes of metabotropic glutamate receptors

Metabotropic or "G-protein coupled" glutamate receptors (mGluRs) were discovered and established as a new type of excitatory amino acid receptor by their unique coupling mechanism (phosphoinositide hydrolysis) and pharmacological characteristics. Recently, the cloning of mGluRs and the availability of selective pharmacological agents has greatly increased knowledge of these receptors. It is now recognized that mGluRs are a highly heterogenous family of glutamate receptors with novel molecular structure that are linked to multiple second messenger pathways. Members of this family have unique pharmacological properties and function to modulate the presynaptic release of glutamate and the post-synaptic sensitivity of the cell to glutamate excitation. New information on mGluRs is elucidating the functions of mGluR subtypes in normal and pathological aspects of neuronal transmission. Basic knowledge of the role of specific mGluRs in CNS function and pathologies will further expand in the near future. This knowledge is providing the framework for the discovery of novel pharmacological approaches to modulate excitatory amino acid neuronal transmission.