GABAB receptor

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gamma-aminobutyric acid (GABA) B receptor, 1
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
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 nervous system and the autonomic division of the peripheral nervous system.[2]

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.[3]


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,[4] gamma-Hydroxybutyric acid (GHB),[5] and possibly in pain.[6] Recent research suggests that these receptors may play an important developmental role.[7]


GABAB Receptors are similar in structure to and in the same receptor family with metabotropic glutamate receptors.[8] There are two subtypes of the receptor, GABAB1 and GABAB2,[9] and these appear to assemble as heterodimers in neuronal membranes by linking up by their intracellular C termini.[8]

It is speculated that binding of GABA causes the subunits to swing shut around the agonist like a venus fly trap.[citation needed]



Positive Allosteric Modulators[edit]


See also[edit]


  1. ^ 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. 
  2. ^ Hyland, NP; Cryan, JF (2010). "A Gut Feeling about GABA: Focus on GABA(B) Receptors". Frontiers in Pharmacology. 1: 124. doi:10.3389/fphar.2010.00124. PMID 21833169. 
  3. ^ 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. 
  4. ^ 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 154371Freely accessible. PMID 12692303. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ a b MRC (Medical Research Council). 2003. Glutamate receptors: Structures and functions. University of Brisotol Centre for Synaptic Plasticity.
  9. ^ 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.
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 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 2574924Freely accessible. PMID 18445779. 
  13. ^ 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. 
  14. ^ 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 2044932Freely accessible. PMID 6652358. 
  15. ^ 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. 
  16. ^ 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. 
  17. ^ Bullock R (January 2005). "SGS-742 Novartis". Current Opinion in Investigational Drugs. 6 (1): 108–13. PMID 15675610. 

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