L-glutamate is the major
excitatory neurotransmitter in the
central nervous system and activates both
ionotropic and
metabotropic glutamate receptors.
Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many
neuropathologic conditions. The metabotropic glutamate receptors are a family of
G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes
GRM1 and
GRM5 and these receptors have been shown to activate phospholipase C. Group II includes
GRM2 and
GRM3 while Group III includes
GRM4,
GRM6,
GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the
cyclic AMP cascade but differ in their agonist selectivities. Alternative
splice variants of GRM8 have been described but their full-length nature has not been determined. == Ligands ==