Metabotropic glutamate receptor 3 (mGlu3) (mGlu3)

The metabotropic glutamate receptor 3 (mGlu3) is a Class C G protein-coupled receptor (GPCR) that serves as a critical modulator of excitatory neurotransmission in the mammalian central nervous system [1, 2]. Encoded by the GRM3 gene, it is primarily coupled to Gi/Go proteins and functions to inhibit adenylyl cyclase, thereby reducing the release of glutamate and other neurotransmitters [2, 12]. Unlike many other glutamate receptors, mGlu3 is widely expressed in both neurons and glial cells, particularly astrocytes, where it facilitates neuroprotection and maintains glutamate homeostasis [1, 19]. It is heavily implicated in the pathophysiology of schizophrenia, bipolar disorder, and major depressive disorder, with genetic variants often linked to cognitive deficits [1, 8]. Therapeutic strategies include the use of mGlu3 agonists for neuroprotection and cognitive enhancement, while negative allosteric modulators (NAMs) are under investigation for rapid antidepressant effects [1, 6]. However, the high structural homology between mGlu3 and the mGlu2 receptor has historically complicated the development of subtype-selective ligands [5, 18].

Other names

GRM3mGluR3Glutamate metabotropic receptor 3GLUR3GPRC1CG protein-coupled receptor family C group 1 member C

Agonism (inhibits glutamate release and provides neuroprotection), Antagonism (potential antidepressant and anti-tumor effects), Positive Allosteric Modulation (PAM), and Negative Allosteric Modulation (NAM).