GABA B receptor.html |
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| Identifiers | |
| Symbol | GABBR1 |
| Entrez | 2550 |
| HUGO | 4070 |
| OMIM | 603540 |
| RefSeq | NM_021905 |
| UniProt | Q9UBS5 |
| Other data | |
| Locus | Chr. 6 p21.3 |
| 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 These receptors are found in the central and peripheral autonomic nervous system.2
Contents |
Functions
They can stimulate the opening of K+ channels which brings the neuron closer to the equilibrium potential of K+, hyperpolarising the neuron. This prevents sodium channels from opening, action potentials from firing, and VDCCs from opening, and so stops neurotransmitter release. Thus GABAB receptors are considered inhibitory receptors.
GABAB receptors can also reduce the activity of adenylyl cyclase and decrease the cell’s conductance to Ca2+.2
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
GABABRs 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 GABAB2,82 and these appear to assemble as heterodimers in neuronal membranes by linking up by their intracellular C termini.27
It is speculated that binding of GABA causes the subunits to swing shut around the agonist like a venus fly trap.2
Selective Ligands
Agonists
- 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
- Phenibut
- CGP-35024: 3-Aminopropyl(methyl)phosphinic acid, CAS# 127729-35-5, 10x more potent than baclofen as GABAB agonist, but also GABAC antagonist
PAMs
Antagonists
- Saclofen
- Phaclofen
- SCH-50911
- 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
See also
References
- ^ Chen K, Li H, Ye N, Zhang J, Wang J (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:. PMID 16182939.
- ^ a b c d e Martin I.L., and Dunn S.M.J. 2002. GABA receptors Tocris Cookson Ltd.
- ^ 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 U S A 100 (9): 5485–90. doi:. 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:. PMID 16129424.
- ^ Manev H, Dimitrijevic N (2004). "Drosophila model for in vivo pharmacological analgesia research". Eur J Pharmacol 491 (2-3): 207–8. doi:. 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:. 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, et al (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. http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11641424.
- ^ Adams CL, Lawrence AJ (2007). "CGP7930: a positive allosteric modulator of the GABAB receptor". CNS Drug Rev 13 (3): 308–16. doi:. PMID 17894647.
- ^ Paterson NE, Vlachou S, Guery S, Kaupmann K, Froestl W, Markou A (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:. PMID 18445779.
- ^ Urwyler S, Pozza MF, Lingenhoehl K, et al (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:. PMID 12954816.
External links
- "GABAB Receptors", IUPHAR Database of Receptors and Ion Channels, International Union of Basic and Clinical Pharmacology, http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1276.