Metabotropic glutamate receptor subtype 2 (mGluR2)

Metabotropic glutamate receptor subtype 2 (mGluR2) is a member of the group II metabotropic glutamate receptors within the class C family of G protein-coupled receptors. It is primarily expressed throughout the central nervous system on both presynaptic and postsynaptic membranes but is especially prominent as a presynaptic autoreceptor on glutamatergic neurons. Activation leads to inhibition of adenylate cyclase via Gi/Go proteins, resulting in decreased cAMP production and reduced neurotransmitter release. mGluR2 plays key roles in modulating synaptic transmission, neuroplasticity, pain perception, emotional processing, and neuroprotection. It has been implicated as a therapeutic target for schizophrenia—where group II agonists show antipsychotic potential—as well as pain disorders and epilepsy. Notably, it also serves as an entry point for rabies virus into neurons. Drugs targeting mGluR2 include orthosteric agonists like LY354740/Eglumegad used experimentally in psychiatric disease models; positive allosteric modulators are under investigation for their ability to fine-tune synaptic signaling with fewer side effects than direct activation.

Other names

mGluR2GRM2 (gene symbol)Group II metabotropic glutamate receptor 2Metabotropic glutamate receptor 2

Agonists activate the Gi/Go pathway to inhibit adenylate cyclase, reducing cAMP levels and suppressing neurotransmitter release presynaptically. Positive allosteric modulators enhance the response to endogenous agonist without directly activating the receptor. Negative allosteric modulators decrease the effect of endogenous agonists or block activation by exogenous ligands.