Metabotropic glutamate receptors in GtoPdb v.2023.1

Metabotropic glutamate (mGlu) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Glutamate Receptors [351]) are a family of G protein-coupled activated neurotransmitter [140]. The mGlu is composed eight members (named mGlu1 to mGlu8) which divided in three groups based similarities agonist pharmacology, primary sequence and protein coupling effector: Group-I (mGlu1 mGlu5), Group-II (mGlu2 mGlu3) Group-III (mGlu4, mGlu6, mGlu7 (see Further reading).Structurally, juxtaposed domains: core protein-activating seven-transmembrane domain (TM), common all GPCRs, linked via rigid cysteine-rich (CRD) Venus Flytrap (VFTD), large bi-lobed extracellular where binds. form constitutive dimers, cross-linked disulfide bridge. structures VFTD mGlu1, mGlu2, mGlu3, mGlu5 have been solved [200, 275, 268, 403]. structure 7 transmembrane (TM) domains both solved, confirm general helical organisation similar that other although helices appear more compacted [88, 433, 62]. Recent advances cryo-electron microscopy provided full-length receptor homodimers [217, 191] heterodimers [91]. Studies revealed possible formation between either group-I receptors, or within group-II -III [89]. First characterised transfected cells, co-localisation specific pharmacological properties suggest existence such brain [270, 440, 145, 283, 259, 218]. Beyond heteromerisation with subtypes, increasing evidence suggests heteromers larger order complexes class A GPCRs (reviewed [140]). endogenous ligands L-glutamic acid, L-serine-O-phosphate, N-acetylaspartylglutamate (NAAG) L-cysteine sulphinic acid. may be 3,5-DHPG (S)-3HPG [30] antagonised (S)-hexylhomoibotenic acid [235]. LY389795 [269], LY379268 eglumegad [354, 434], DCG-IV (2R,3R)-APDC [355], eGlu [170] LY307452 [425, 105]. L-AP4 (R,S)-4-PPG [130]. An example an antagonist selective for LY341495, blocks mGlu2 mGlu3 at low nanomolar concentrations, mGlu8 high mGlu4, mGlu5, micromolar range [185]. In addition orthosteric directly interact recognition site, allosteric modulators bind TM described. Negative listed separately. positive most often act ‘potentiators’ response, without significantly activating absence agonist.