Group II metabotropic glutamate receptor (Group II mGluR)

The **Group II metabotropic glutamate receptor** family consists of two G protein-coupled receptor (GPCR) subtypes, mGluR2 and mGluR3, encoded by the genes GRM2 and GRM3. These receptors are characterized by their large extracellular ligand-binding domains and their classical 7-transmembrane structure typical of Class C GPCRs. Coupled predominantly to G_i/o proteins, these receptors mediate inhibition of adenylyl cyclase and modulate voltage-dependent ion channels, thus regulating neurotransmitter release and neuronal excitability throughout the central nervous system. Group II mGluRs act as autoreceptors at glutamatergic synapses and as heteroreceptors at GABAergic and other synapses. They are expressed in regions involved in cognition, emotion, pain processing, and are present in both neurons and glial cells depending on the subtype. These receptors are considered promising therapeutic targets for psychiatric disorders (such as schizophrenia), pain, and certain cancers, with several drugs in development targeting their modulation.

Other names

Group II mGluRmGluR2/3mGlu2/3 receptormetabotropic glutamate receptor 2 and 3GRM2/GRM3

Orthosteric agonism (activation by glutamate analogs/agonists) Positive allosteric modulation (PAMs increase receptor response to endogenous glutamate) Negative allosteric modulation (NAMs decrease response to endogenous ligand) Inhibition of adenylyl cyclase via G_i/o coupling Modulation of pre- and postsynaptic neurotransmitter release