GHB receptor

G protein-coupled receptor 172A
Identifiers
Symbol GPR172A
Entrez 79581
HUGO 30224
OMIM 607882
RefSeq NM_024531
UniProt Q9HAB3
Other data
Locus Chr. 8 q24.3

The γ-hydroxybutyrate (GHB) receptor (GHBR), originally identified as GPR172A, is a G protein-coupled receptor (GPCR) that binds the neurotransmitter and psychoactive drug γ-hydroxybutyric acid (GHB).

History

The existence of a specific GHB receptor was predicted by observing the action of GHB and related compounds that primarily act on the GABAB receptor, but also exhibit a range of effects which were found not to be produced by GABAB activity, and so were suspected of being produced by a novel and at the time unidentified receptor target. Following the discovery of the "orphan" G-protein coupled receptor GPR172A, it was subsequently found to be the GHB receptor whose existence had been previously predicted.[1] The rat GHB receptor was first cloned and characterised in 2003[2] followed by the human receptor in 2007.[3]

Function

The function of the GHB receptor appears to be quite different from that of the GABAB receptor. It shares no sequence homology with GABAB, and administration of mixed GHB/GABAB receptor agonists along with a selective GABAB antagonist or selective agonists for the GHB receptor which are not agonists at GABAB, do not produce a sedative effect, instead causing a stimulant effect followed by convulsions at higher doses, thought to be mediated through increased Na+/K+ current and increased release of dopamine and glutamate.[4][5][6][7][8][9]

Ligands

Agonists

Antagonists

Unknown/unclear

References

  1. ↑ Snead OC (November 2000). "Evidence for a G protein-coupled gamma-hydroxybutyric acid receptor". J. Neurochem. 75 (5): 1986–96. doi:10.1046/j.1471-4159.2000.0751986.x. PMID 11032888.
  2. ↑ Andriamampandry C, Taleb O, Viry S, et al. (September 2003). "Cloning and characterization of a rat brain receptor that binds the endogenous neuromodulator gamma-hydroxybutyrate (GHB)". FASEB J. 17 (12): 1691–3. doi:10.1096/fj.02-0846fje. PMID 12958178.
  3. ↑ Andriamampandry C, Taleb O, Kemmel V, Humbert JP, Aunis D, Maitre M (March 2007). "Cloning and functional characterization of a gamma-hydroxybutyrate receptor identified in the human brain". FASEB J. 21 (3): 885–95. doi:10.1096/fj.06-6509com. PMID 17197387.
  4. ↑ Cash, C; Gobaille, S; Kemmel, V; Andriamampandry, C; Maitre, M (1999). "γ-hydroxybutyrate receptor function studied by the modulation of nitric oxide synthase activity in rat frontal cortex punches". Biochemical Pharmacology. 58 (11): 1815–9. doi:10.1016/S0006-2952(99)00265-8. PMID 10571257.
  5. ↑ Maitre M, Humbert JP, Kemmel V, Aunis D, Andriamampandry C (March 2005). "[A mechanism for gamma-hydroxybutyrate (GHB) as a drug and a substance of abuse]" [A mechanism for gamma-hydroxybutyrate (GHB) as a drug and a substance of abuse]. Med Sci (Paris) (in French). 21 (3): 284–9. doi:10.1051/medsci/2005213284. PMID 15745703.
  6. ↑ Castelli MP, Ferraro L, Mocci I, et al. (November 2003). "Selective gamma-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of gamma-hydroxybutyric acid". J. Neurochem. 87 (3): 722–32. doi:10.1046/j.1471-4159.2003.02037.x. PMID 14535954.
  7. ↑ Castelli MP (November 2008). "Multi-faceted aspects of gamma-hydroxybutyric Acid: a neurotransmitter, therapeutic agent and drug of abuse". Mini Rev Med Chem. 8 (12): 1188–202. doi:10.2174/138955708786141025. PMID 18855733.
  8. ↑ Crunelli V, Emri Z, Leresche N (February 2006). "Unravelling the brain targets of γ-hydroxybutyric acid". Curr Opin Pharmacol. 6 (1): 44–52. doi:10.1016/j.coph.2005.10.001. PMC 2174623Freely accessible. PMID 16368267.
  9. ↑ Carter LP, Koek W, France CP (October 2008). "Behavioral Analyses of GHB: Receptor Mechanisms". Pharmacol. Ther. 121 (1): 100–14. doi:10.1016/j.pharmthera.2008.10.003. PMC 2631377Freely accessible. PMID 19010351.
  10. ↑ Ticku MK, Mehta AK (October 2008). "Characterization and pharmacology of the GHB receptor". Annals of the New York Academy of Sciences. 1139: 374–85. doi:10.1196/annals.1432.048. PMID 18991884.
  11. ↑ Absalom N, Eghorn LF, Villumsen IS, Karim N, Bay T, Olsen JV, Knudsen GM, Bräuner-Osborne H, Frølund B, Clausen RP, Chebib M, Wellendorph P (2012). "α4βδ GABA(A) receptors are high-affinity targets for γ-hydroxybutyric acid (GHB)". Proc. Natl. Acad. Sci. U.S.A. 109 (33): 13404–9. doi:10.1073/pnas.1204376109. PMC 3421209Freely accessible. PMID 22753476.
  12. ↑ Høg S, Wellendorph P, Nielsen B, et al. (2008). "Novel High-Affinity and Selective Biaromatic 4-Substituted gamma-Hydroxybutyric Acid (GHB) Analogues as GHB Ligands: Design, Synthesis, and Binding Studies". J. Med. Chem. 51 (24): 8088–95. doi:10.1021/jm801112u. PMID 19053823.


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