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{{infobox protein
|Name= G  protein-coupled receptor 172A
|caption=
|image=
|width=
|HGNCid = 30224
|Symbol = GPR172A
|AltSymbols =
|EntrezGene = 79581
|OMIM=607882
|RefSeq = NM_024531
|UniProt = Q9HAB3
|PDB =
|ECnumber =
|Chromosome = 8
|Arm= q
|Band= 24.3
|LocusSupplementaryData =
}}


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).


'''Gamma-hydroxybutyrate receptor''' or '''GHB receptor''' is a receptor that binds [[gamma-Hydroxybutyric acid]]. Its existence was predicted by observing the action of its agonists that previously were thought to act on GABA-B receptors.<!--
==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|GABA<sub>B</sub> receptor]], but also exhibit a range of effects which were found not to be produced by GABA<sub>B</sub> 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.<ref name="pmid11032888">{{cite journal |author=Snead OC |title=Evidence for a G protein-coupled gamma-hydroxybutyric acid receptor |journal=J. Neurochem. |volume=75 |issue=5 |pages=1986–96 |date=November 2000 |pmid=11032888 |doi= 10.1046/j.1471-4159.2000.0751986.x |url= }}</ref> The rat GHB receptor was first cloned and characterised in 2003<ref name="pmid12958178">{{cite journal |vauthors=Andriamampandry C, Taleb O, Viry S |title=Cloning and characterization of a rat brain receptor that binds the endogenous neuromodulator gamma-hydroxybutyrate (GHB) |journal= FASEB J. |volume=17 |issue=12 |pages=1691–3 |date=September 2003 |pmid=12958178 |doi=10.1096/fj.02-0846fje |url=|display-authors=etal}}</ref> followed by the human receptor in 2007.<ref name="pmid17197387">{{cite journal |vauthors=Andriamampandry C, Taleb O, Kemmel V, Humbert JP, Aunis D, Maitre M |title=Cloning and functional characterization of a gamma-hydroxybutyrate receptor identified in the human brain |journal=FASEB J. |volume=21 |issue=3 |pages=885–95 |date=March 2007 |pmid=17197387 |doi=10.1096/fj.06-6509com |url=}}</ref>


--><ref name="pmid11032888">{{cite journal |author=Snead OC |title=Evidence for a G protein-coupled gamma-hydroxybutyric acid receptor |journal=[[J. Neurochem.]] |volume=75 |issue=5 |pages=1986–96 |year=2000 |month=November |pmid=11032888 |doi= |url=http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=2000&volume=75&issue=5&spage=1986 |issn=}}</ref><!--
==Function==
The function of the GHB receptor appears to be quite different from that of the GABA<sub>B</sub> receptor. It shares no [[sequence homology]] with GABA<sub>B</sub>, and administration of mixed GHB/GABA<sub>B</sub> receptor agonists along with a selective GABA<sub>B</sub> antagonist or selective agonists for the GHB receptor which are not agonists at GABA<sub>B</sub>, do not produce a sedative effect, instead causing a stimulant effect followed by [[convulsion]]s at higher doses, thought to be mediated through increased Na<sup>+</sup>/K<sup>+</sup> current and increased release of [[dopamine]] and [[glutamate]].<ref>{{cite journal | doi = 10.1016/S0006-2952(99)00265-8 | title = γ-hydroxybutyrate receptor function studied by the modulation of nitric oxide synthase activity in rat frontal cortex punches | year = 1999 | author = Cash, C | journal = [[Biochemical Pharmacology (journal)|Biochemical Pharmacology]] | volume = 58 | pages = 1815–9 | pmid = 10571257 | issue = 11 | last2 = Gobaille | first2 = S | last3 = Kemmel | first3 = V | last4 = Andriamampandry | first4 = C | last5 = Maitre | first5 = M  }}</ref><ref name="mechanism">{{cite journal |vauthors=Maitre M, Humbert JP, Kemmel V, Aunis D, Andriamampandry C |title=[A mechanism for gamma-hydroxybutyrate (GHB) as a drug and a substance of abuse] |language=French |journal=Med Sci (Paris) |volume=21 |issue=3 |pages=284–9 |date=March 2005 |pmid=15745703 |doi=10.1051/medsci/2005213284 |url=http://www.edk.fr/reserve/revues/ms_papier/e-docs/00/00/06/F7/document_article.md |trans-title=A mechanism for gamma-hydroxybutyrate (GHB) as a drug and a substance of abuse |deadurl=yes |archiveurl=https://web.archive.org/web/20090715112705/http://www.edk.fr/reserve/revues/ms_papier/e-docs/00/00/06/F7/document_article.md |archivedate=2009-07-15 |df= }}</ref><ref name = "nsngtu">{{cite journal |vauthors=Castelli MP, Ferraro L, Mocci I |title=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 |journal=J. Neurochem. |volume=87 |issue=3 |pages=722–32 |date=November 2003 |pmid=14535954 |doi= 10.1046/j.1471-4159.2003.02037.x|url=|display-authors=etal}}</ref><ref name="pmid18855733">{{cite journal | author = Castelli MP | title = Multi-faceted aspects of gamma-hydroxybutyric Acid: a neurotransmitter, therapeutic agent and drug of abuse | journal = Mini Rev Med Chem | volume = 8 | issue = 12 | pages = 1188–202 |date=November 2008 | pmid = 18855733 | doi = 10.2174/138955708786141025| url = }}</ref><ref name="pmid16368267">{{cite journal |vauthors=Crunelli V, Emri Z, Leresche N | title = Unravelling the brain targets of γ-hydroxybutyric acid | journal = Curr Opin Pharmacol | volume = 6 | issue = 1 | pages = 44–52 |date=February 2006 | pmid = 16368267 | pmc = 2174623 | doi = 10.1016/j.coph.2005.10.001 | url =  }}</ref><ref name="pmid19010351">{{cite journal |vauthors=Carter LP, Koek W, France CP | title = Behavioral Analyses of GHB: Receptor Mechanisms | journal = Pharmacol. Ther. | volume = 121| issue = 1| pages = 100–14|date=October 2008 | pmid = 19010351 | doi = 10.1016/j.pharmthera.2008.10.003 | url = | pmc = 2631377  }}</ref>


-->  The rat GHB receptor was first cloned and characterised in [[2003]]<!--
==Ligands==


--><ref name="pmid12958178">{{cite journal |author=Andriamampandry C, Taleb O, Viry S, ''et al'' |title=Cloning and characterization of a rat brain receptor that binds the endogenous neuromodulator gamma-hydroxybutyrate (GHB) |journal=[[FASEB J.]] |volume=17 |issue=12 |pages=1691–3 |year=2003 |month=September |pmid=12958178 |doi=10.1096/fj.02-0846fje |url=http://www.fasebj.org/cgi/pmidlookup?view=long&pmid=12958178}}</ref><!--
===Agonists===
* [[1,4-Butanediol]]
* [[HOCPCA|3-Hydroxycyclopent-1-enecarboxylic acid]] (HOCPCA)
* [[4-(p-Chlorobenzyl)-GHB|4-(''p''-Chlorobenzyl)-GHB]]
* [[γ-Butyrolactone]] (GBL)
* [[gamma-Hydroxybutyric acid|γ-Hydroxybutyric acid]] (GHB)
* [[gamma-Hydroxyvaleric acid|γ-Hydroxyvaleric acid]] (GHV; 4-methyl-GHB)
* [[gamma-Valerolactone|γ-Valerolactone]] (GVL)
* [[T-HCA|''trans''-Hydroxycrotonic acid]] (T-HCA)
* [[Aceburic acid]]
* [[NCS-356]] (4-(4-chlorophenyl)-4-hydroxy-but-2-enoic acid, CAS# 430440-66-7)
* [[NCS-435]] (4-(''p''-methoxybenzyl)-GHB)
* [[UMB66]]
* [[4-Hydroxy-4-methylpentanoic acid|UMB68]]
* [[UMB72]]
* [[UMB86]]<ref name="pmid18991884">{{cite journal |vauthors=Ticku MK, Mehta AK |title=Characterization and pharmacology of the GHB receptor |journal=Annals of the New York Academy of Sciences |volume=1139 |issue= |pages=374–85 |date=October 2008 |pmid=18991884 |doi=10.1196/annals.1432.048 |url=}}</ref>


--> followed by the human receptor in 2007.<!--
===Antagonists===
* [[Gabazine]] (SR-95531)<ref name="pmid22753476">{{cite journal | vauthors = 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 | title = α4βδ GABA(A) receptors are high-affinity targets for γ-hydroxybutyric acid (GHB) | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 109 | issue = 33 | pages = 13404–9 | year = 2012 | pmid = 22753476 | pmc = 3421209 | doi = 10.1073/pnas.1204376109 | url = }}</ref>
* [[NCS-382]]


--><ref name="pmid17197387">{{cite journal |author=Andriamampandry C, Taleb O, Kemmel V, Humbert JP, Aunis D, Maitre M |title=Cloning and functional characterization of a gamma-hydroxybutyrate receptor identified in the human brain |journal=[[FASEB J.]] |volume=21 |issue=3 |pages=885–95 |year=2007 |month=March |pmid=17197387 |doi=10.1096/fj.06-6509com |url=http://www.fasebj.org/cgi/pmidlookup?view=long&pmid=17197387}}</ref> It is a [[G-protein coupled receptor]].
===Unknown/unclear===
* (''R'')-4-[4′-(2-Iodobenzyloxy)phenyl]-GHB]]<ref name="pmid19053823">{{cite journal |vauthors=Høg S, Wellendorph P, Nielsen B |title=Novel High-Affinity and Selective Biaromatic 4-Substituted gamma-Hydroxybutyric Acid (GHB) Analogues as GHB Ligands: Design, Synthesis, and Binding Studies |journal=J. Med. Chem. |volume= 51|issue= 24|pages= 8088–95|year=2008 |pmid=19053823 |doi=10.1021/jm801112u |url=|display-authors=etal}}</ref>
* [[Amisulpride]]
* [[Levosulpiride]]
* [[Prochlorperazine]]
* [[Sulpiride]]
* [[Sultopride]]


== See also ==
==References==
* [[gamma-Hydroxybutyric acid]]
{{Reflist|2}}


== References ==
{{G protein-coupled receptors}}
{{reflist|2}}
{{GHBergics}}


[[Category:receptors]]
[[Category:G protein coupled receptors]]
[[Category:GHB]]


{{WH}}
 
{{WS}}
{{genetics-stub}}
{{receptor-stub}}

Revision as of 22:31, 15 November 2017

G protein-coupled receptor 172A
Identifiers
SymbolGPR172A
Entrez79581
HUGO30224
OMIM607882
RefSeqNM_024531
UniProtQ9HAB3
Other data
LocusChr. 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. Archived from the original on 2009-07-15.
  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 2174623. 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 2631377. 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 3421209. 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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