GHB receptor
Gama-hidroksibuteratni receptor, ili GHB receptor (GHBR), originalno identifikovan kao GPR172A, je G protein-spregnuti receptor koji vezuje gama-hidroksibuternu kiselinu (GHB).
| G protein-spregnuti receptor 172A | |
|---|---|
| Identifikatori | |
| Simbol | GPR172A |
| Entrez | 79581 |
| HUGO | 30224 |
| OMIM | 607882 |
| RefSeq | NM_024531 |
| UniProt | Q9HAB3 |
| Drugi podaci | |
| Lokus | Hromozom 8 q24.3 |
Istorija uredi
Postojanje specifičnog GHB receptora je bilo predviđeno na osnovu proučavanja dejstva GHB i srodnih jedinjenja, koja prvenstveno deluju na GABAB receptore, ali takođe pokazuju niz efekata za koje je nađeno da nisu posledica GABAB aktivnosti. Iz tog razloga se smatralo da su proizvedeni jednim od neidentifikovanih receptora. Nakon otkrića orfan G-protein spregnutog receptora GPR172A, utvrđeno je da je on zapravo GHB receptor.[1] GHB receptor pacova je prvi put bio kloniran i karakterisan 2003[2], a tome je sledila ljudska izoforma 2007.[3]
Funkcija uredi
Funkcija GHB receptora se znatno razlikuje od funkcije GABAB receptora. GHBR nema homolognu sekvencu sa GABAB receptorom, i selektivni agonisti za GHB receptor nisu agonisti GABAB receptora. Administracija nespecifičnih GHBR/GABAB agonista zajedno sa selektivnim GABAB antagonistom, ne proizvodi sedativni efekat, umesto toga izaziva stimulišući efekat, čemu slede konvulzije na višim dozama, što se smatra da je posredovano povećanjem Na+/K+ struje i povišenim oslobađanjem dopamina i glutamata.[4][5][6][7][8][9]
Selektivni ligandi uredi
- (R)-4-[4′-(2-jodobenziloksi)fenil]-GHB[10]
Agonisti uredi
- gama-hidroksibuterna kiselina
- trans-hidroksikrotonska kiselina
- UMB66
- UMB68
- UMB72
- UMB86[11]
- (R)-3-hidroksiciklopent-1-enekarboksilna kiselina
- NCS-356: 4-(4-hlorofenil)-4-hidroksi-but-2-enoiska kiselina
- NCS-435: 4-(p-metoksibenzil)-GHB
- 4-(p-hlorobenzil)-GHB
Antagonisti uredi
Literatura uredi
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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]] (French). Med Sci (Paris) 21 (3): 284–9. PMID 15745703. Arhivirano iz originala na datum 2009-07-15. Pristupljeno 2014-05-08.
- ↑ 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.
- ↑ 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.
- ↑ Crunelli V, Emri Z, Leresche N (February 2006). „Unravelling the brain targets of gamma-hydroxybutyric acid”. Curr Opin Pharmacol 6 (1): 44–52. DOI:10.1016/j.coph.2005.10.001. PMC 2174623. PMID 16368267.
- ↑ 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.
- ↑ 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.
- ↑ 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.