mGluR2

mGluR2, or metabotropic glutamate receptor 2, is a G protein-coupled receptor that belongs to the group II subset of metabotropic glutamate receptors. It is encoded by the GRM2 gene in humans. In the brain, mGluR2 is primarily expressed presynaptically and is found throughout the central nervous system, with relatively high expression in cortical and limbic regions. It often coexists with other group II receptors (notably mGluR3) to regulate neurotransmission.

Function and mechanism: As a Gi/o-coupled receptor, mGluR2 activation inhibits adenylyl cyclase, reduces cAMP formation, and modulates voltage-gated calcium channels. This leads to decreased release of glutamate and other neurotransmitters from presynaptic terminals, contributing to the regulation of synaptic excitability and plasticity. mGluR2 can form homodimers or heterodimers with other metabotropic glutamate receptors, influencing signaling properties.

Pharmacology and clinical relevance: Glutamate is the endogenous ligand. Pharmacological tools include selective agonists such as LY379268 and LY354740, used in research to activate group II mGluRs. Blockade with antagonists or genetic deletion of GRM2 alters neurotransmission and behavior in animal models. Therapeutic interest has focused on mGluR2/3 as potential targets for schizophrenia, anxiety, addiction, and pain, with various agonists and allosteric modulators under investigation. The clinical utility remains under study, and results have been variable.