Metabotropic glutamate receptors

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).


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Metabotropic glutamate (mGlu) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Metabotropic Glutamate Receptors [62]) are activated by the endogenous ligands L-glutamic acid, L-serine-O-phosphate, N-acetylaspartylglutamate (NAAG) and L-cysteine sulphinic acid. Examples of agonists selective for mGlu receptors compared with ionotropic glutamate receptors are (1S,3R)-ACPD and L-CCG-I, which show limited selectivity for Group-II receptors. An example of an antagonist selective for mGlu receptors is LY341495, which blocks mGlu2 and mGlu3 at low nanomolar concentrations, mGlu8 at high nanomolar concentrations, and mGlu4, mGlu5, and mGlu7 in the micromolar range [28]. Three groups of native receptors are distinguishable on the bases of similarities of agonist pharmacology, primary sequence and G protein coupling to effector: Group-I (mGlu1 and mGlu5), Group-II (mGlu2 and mGlu3) and Group-III (mGlu4, mGlu6, mGlu7 and mGlu8) (see Further reading). Group-I mGlu receptors may be activated by 3,5-DHPG and (S)-3HPG [5] and antagonized by (S)-hexylhomoibotenic acid [39]. Group-II mGlu receptors may be activated by LY389795 [47], LY379268 [47], eglumegad [63,74], DCG-IV and (2R,3R)-APDC [64], and antagonised by eGlu (4.3, [25] and LY307452 [17,72]. Group-III mGlu receptors may be activated by L-AP4 and (R,S)-4-PPG [20].

In addition to orthosteric ligands that directly interact with the glutamate recognition site directly, allosteric modulators have been described. Negative allosteric modulators are listed separately. The positive allosteric modulators most often act as ‘potentiators’ of an orthosteric agonist response, without significantly activating the receptor in the absence of agonist.

Although mGlu receptors have been thought to only form homodimers, recent studies revealed the possible formation of heterodimers between either group-I receptors, or within and between group-II and -III receptors [15]. Although well characterized in transfected cells, co-localization and specific pharmacological properties also suggest the existence of such heterodimers in the brain [75].

The structure of the 7 transmembrane (TM) domains of both mGlu1 and mGlu5 have been solved, and confirm a general helical organization similar to that of other GPCRs, although the helices appear more compacted [14,73].


mGlu1 receptor Show summary » More detailed page

mGlu2 receptor Show summary » More detailed page

mGlu3 receptor Show summary » More detailed page

mGlu4 receptor Show summary » More detailed page

mGlu5 receptor Show summary » More detailed page

mGlu6 receptor Show summary » More detailed page

mGlu7 receptor Show summary » More detailed page

mGlu8 receptor Show summary » More detailed page


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Further reading

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NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation:

Cyril Goudet, Francine Acher, P. Jeffrey Conn, Robert Duvoisin, Francesco Ferraguti, Peter J. Flor, David Hampson, Michael P. Johnson, Yoshihiro Kubo, James Monn, Shigetada Nakanishi, Ferdinando Nicoletti, Jean-Philippe Pin, Darryle D. Schoepp, Ryuichi Shigemoto, Michihiro Tateyama. Metabotropic glutamate receptors. Accessed on 21/02/2017. IUPHAR/BPS Guide to PHARMACOLOGY,

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Davenport AP, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: G protein-coupled receptors. Br J Pharmacol. 172: 5744-5869.