Metabotropic glutamate receptor

The mGluRs perform a variety of functions in the central and peripheral nervous systems: For example, they are involved in learning, memory, anxiety, and the perception of pain.

[2] They are found in pre- and postsynaptic neurons in synapses of the hippocampus, cerebellum,[3] and the cerebral cortex, as well as other parts of the brain and in peripheral tissues.

[4][16] Stimulating the receptors causes the associated enzyme phospholipase C to hydrolyze phosphoinositide phospholipids in the cell's plasma membrane.

The lipophilic diacylglycerol remains in the membrane, acting as a cofactor for the activation of protein kinase C. These receptors are also associated with Na+ and K+ channels.

The receptors in group II, including mGluRs 2 and 3, and group III, including mGluRs 4, 6, 7, and 8, (with some exceptions) prevent the formation of cyclic adenosine monophosphate, or cAMP, by activating a G protein that inhibits the enzyme adenylyl cyclase, which forms cAMP from ATP.

Receptors in groups II and III reduce the activity of postsynaptic potentials, both excitatory and inhibitory, in the cortex.

[15] Group II[25] and III[23] mGluRs tend to protect neurons from excitotoxicity,[15][26][27] possibly by reducing the activity of NMDARs.

[17] Since metabotropic glutamate receptors are involved in a variety of functions, abnormalities in their expression can contribute to disease.

[33] Most recently, Group I mGluRs, have been implicated in the pathogenesis of Fragile X, a type of autism,[34] and a number of studies are currently testing the therapeutic potential of drugs that modify these receptors.

[35] There is also growing evidence that group II metabotropic glutamate receptor agonists may play a role in the treatment of schizophrenia.

[37] The drug LY354740 (also known as Eglumegad, an mGlu2/3 agonist) was shown to attenuate physiologic and cognitive abnormalities in animal and human studies of NMDA receptor antagonist and serotonergic hallucinogen effects,[38][39][40][41] supporting the subsequent clinical evidence of efficacy for an mGluR2/3 agonist in the treatment of schizophrenia.

[42] The same drug has been shown to interfere in the hypothalamic–pituitary–adrenal axis, with chronic oral administration of this drug leading to markedly reduced baseline cortisol levels in bonnet macaques (Macaca radiata); acute infusion of LY354740 resulted in a marked diminution of yohimbine-induced stress response in those animals.