GABAB receptor
| gamma-aminobutyric acid (GABA) B receptor, 1 | |
|---|---|
| Identifiers | |
| Symbol | GABBR1 |
| Entrez | 2550 |
| HUGO | 4070 |
| OMIM | 603540 |
| RefSeq | NM_021905 |
| UniProt | Q9UBS5 |
| Other data | |
| Locus | Chr. 6 p21.3 |
| gamma-aminobutyric acid (GABA) B receptor, 2 | |
|---|---|
| Identifiers | |
| Symbol | GABBR2 |
| Alt. symbols | GPR51 |
| Entrez | 9568 |
| HUGO | 4507 |
| OMIM | 607340 |
| RefSeq | NM_005458 |
| UniProt | O75899 |
| Other data | |
| Locus | Chr. 9 q22.1-22.3 |
GABAB receptors (GABABR) are metabotropic transmembrane receptors for gamma-aminobutyric acid (GABA) that are linked via G-proteins to potassium channels.[1] The changing potassium concentrations hyperpolarize the cell at the end of an action potential. The reversal potential of the GABAB-mediated IPSP is -100 mV, which is much more hyperpolarized than the GABAA IPSP. GABAB receptors are found in the central as well as in the autonomic division of the peripheral nervous system.[citation needed]
The receptors were first named in 1981 when their distribution in the CNS was determined, which was determined by Norman Bowery and his team using radioactively labelled baclofen.[2]
Contents
Functions[edit]
They can stimulate the opening of K+ channels which brings the neuron closer to the equilibrium potential of K+. This reduces the frequency of action potentials which reduces neurotransmitter release.[citation needed] Thus GABAB receptors are considered inhibitory receptors.[by whom?]
GABAB receptors can also reduce the activity of adenylyl cyclase and decrease the cell’s conductance to Ca2+.[citation needed]
GABAB receptors are involved in behavioral actions of ethanol,[3] gamma-Hydroxybutyric acid (GHB),[4] and possibly in pain.[5] Recent research suggests that these receptors may play an important developmental role.[6]
Structure[edit]
GABAB Receptors are similar in structure to and in the same receptor family with metabotropic glutamate receptors.[7] There are two subtypes of the receptor, GABAB1 and GABAB2,[8] and these appear to assemble as heterodimers in neuronal membranes by linking up by their intracellular C termini.[7]
It is speculated that binding of GABA causes the subunits to swing shut around the agonist like a venus fly trap.[citation needed]
Ligands[edit]
Agonists[edit]
- GABA
- Baclofen is a GABA analogue which acts as a selective agonist of GABAB receptors, and is used as a muscle relaxant. However, it can aggravate absence seizures, and so is not used in epilepsy.
- gamma-Hydroxybutyrate (GHB)
- Phenibut
- Isovaline
- 3-Aminopropylphosphinic acid
- Lesogaberan
- SKF-97541: 3-Aminopropyl(methyl)phosphinic acid, 10x more potent than baclofen as GABAB agonist, but also GABAC antagonist
- CGP-44532
Positive Allosteric Modulators[edit]
Antagonists[edit]
- Homotaurine [13]
- Ginsenosides [14]
- 2-OH-saclofen
- Fasoracetam[citation needed]
- Saclofen
- Phaclofen
- SCH-50911
- 2-Phenethylamine
- CGP-35348
- CGP-52432: 3-([(3,4-Dichlorophenyl)methyl]amino]propyl) diethoxymethyl)phosphinic acid, CAS# 139667-74-6
- CGP-55845: (2S)-3-([(1S)-1-(3,4-Dichlorophenyl)ethyl]amino-2-hydroxypropyl)(phenylmethyl)phosphinic acid, CAS# 149184-22-5
- SGS-742 [15][16]
See also[edit]
References[edit]
- ^ Chen K, Li HZ, Ye N, Zhang J, Wang JJ (2005). "Role of GABAB receptors in GABA and baclofen-induced inhibition of adult rat cerebellar interpositus nucleus neurons in vitro". Brain Res Bull. 67 (4): 310–8. doi:10.1016/j.brainresbull.2005.07.004. PMID 16182939.
- ^ Hill, DR; Bowery, NG (12 March 1981). "3H-baclofen and 3H-GABA bind to bicuculline-insensitive GABA B sites in rat brain.". Nature. 290 (5802): 149–52. doi:10.1038/290149a0. PMID 6259535.
- ^ Dzitoyeva S, Dimitrijevic N, Manev H (2003). "Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence". Proc Natl Acad Sci USA. 100 (9): 5485–90. Bibcode:2003PNAS..100.5485D. doi:10.1073/pnas.0830111100. PMC 154371
. PMID 12692303. - ^ Dimitrijevic N, Dzitoyeva S, Satta R, Imbesi M, Yildiz S, Manev H (2005). "Drosophila GABA(B) receptors are involved in behavioral effects of gamma-hydroxybutyric acid (GHB)". Eur J Pharmacol. 519 (3): 246–52. doi:10.1016/j.ejphar.2005.07.016. PMID 16129424.
- ^ Manev H, Dimitrijevic N (2004). "Drosophila model for in vivo pharmacological analgesia research". Eur J Pharmacol. 491 (2–3): 207–8. doi:10.1016/j.ejphar.2004.03.030. PMID 15140638.
- ^ Dzitoyeva S, Gutnov A, Imbesi M, Dimitrijevic N, Manev H (2005). "Developmental role of GABAB(1) receptors in Drosophila". Brain Res Dev Brain Res. 158 (1–2): 111–4. doi:10.1016/j.devbrainres.2005.06.005. PMID 16054235.
- ^ a b MRC (Medical Research Council). 2003. Glutamate receptors: Structures and functions. University of Brisotol Centre for Synaptic Plasticity.
- ^ Purves D., Augustine G.J., Fitzpatrick D., Katz L.C., LaMantia A.S., McNamara J.O., and Williams S.M. 2001. Neuroscience, Second Edition. Sinauer Associates, Inc.
- ^ Urwyler S, Mosbacher J, Lingenhoehl K, Heid J, Hofstetter K, Froestl W, Bettler B, Kaupmann K (November 2001). "Positive allosteric modulation of native and recombinant gamma-aminobutyric acid(B) receptors by 2,6-Di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and its aldehyde analog CGP13501". Mol. Pharmacol. 60 (5): 963–71. PMID 11641424.
- ^ Adams CL, Lawrence AJ (2007). "CGP7930: a positive allosteric modulator of the GABAB receptor". CNS Drug Rev. 13 (3): 308–16. doi:10.1111/j.1527-3458.2007.00021.x. PMID 17894647.
- ^ Paterson NE, Vlachou S, Guery S, Kaupmann K, Froestl W, Markou A (July 2008). "Positive modulation of GABA(B) receptors decreased nicotine self-administration and counteracted nicotine-induced enhancement of brain reward function in rats". J. Pharmacol. Exp. Ther. 326 (1): 306–14. doi:10.1124/jpet.108.139204. PMC 2574924. PMID 18445779.
- ^ Urwyler S, Pozza MF, Lingenhoehl K, Mosbacher J, Lampert C, Froestl W, Koller M, Kaupmann K (October 2003). "N,N'-Dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine (GS39783) and structurally related compounds: novel allosteric enhancers of gamma-aminobutyric acidB receptor function". J. Pharmacol. Exp. Ther. 307 (1): 322–30. doi:10.1124/jpet.103.053074. PMID 12954816.
- ^ Giotti A, Luzzi S, Spagnesi S, Zilletti L (1983). "Homotaurine: a GABAB antagonist in guinea-pig ileum.". Br. J. Pharmacol. 79: 855–62. doi:10.1111/j.1476-5381.1983.tb10529.x. PMC 2044932. PMID 6652358.
- ^ Kimura T, Saunders PA, Kim HS, Rheu HM, Oh KW, Ho IK (1994). "Interactions of ginsenosides with ligand-bindings of GABA(A) and GABA(B) receptors". General Pharmacology. 25 (1): 193–9. doi:10.1016/0306-3623(94)90032-9. PMID 8026706.
- ^ Froestl W, Gallagher M, Jenkins H, Madrid A, Melcher T, Teichman S, Mondadori CG, Pearlman R (October 2004). "SGS742: the first GABA(B) receptor antagonist in clinical trials". Biochemical Pharmacology. 68 (8): 1479–87. doi:10.1016/j.bcp.2004.07.030. PMID 15451390.
- ^ Bullock R (January 2005). "SGS-742 Novartis". Current Opinion in Investigational Drugs (London, England : 2000). 6 (1): 108–13. PMID 15675610.
