GABAB receptor

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gamma-aminobutyric acid (GABA) B receptor, 1
NCBI gene2550
Other data
LocusChr. 6 p21.3
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gamma-aminobutyric acid (GABA) B receptor, 2
Alt. symbolsGPR51
NCBI gene9568
Other data
LocusChr. 9 q22.1-22.3
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GABAB receptors (GABABR) are G-protein coupled receptors for gamma-aminobutyric acid (GABA), therefore making them metabotropic receptors, 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 (inhibitory postsynaptic potential) 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]


GABABRs stimulate the opening of K+ channels, specifically GIRKs, 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 inhibitory receptors.

GABAB receptors also reduces the activity of adenylyl cyclase and Ca2+ channels by using G-proteins with Gi/G0 α subunits.[4]

GABAB receptors are involved in behavioral actions of ethanol,[5][6] gamma-hydroxybutyric acid (GHB),[7] and possibly in pain.[8] Recent research suggests that these receptors may play an important developmental role.[9]

Receptor dimer, inactive apo state, cartoon representation


GABAB Receptors are similar in structure to and in the same receptor family with metabotropic glutamate receptors.[10] There are two subunits of the receptor, GABAB1 and GABAB2,[11] and these appear to assemble as obligate heterodimers in neuronal membranes by linking up by their intracellular C termini.[10] In the mammalian brain, two predominant, differentially expressed isoforms of the GABAB1 are transcribed from the Gabbr1 gene, GABAB(1a) and GABAB(1b), which are conserved in different species including humans.[12] This might potentially offer more complexity in terms of the function due to different composition of the receptor.[12] Cryo-electron microscopy structures of the full length GABAB receptor in different conformational states from inactive apo to fully active have been obtained. Unlike Class A and B GPCRs, phospholipids bind within the transmembrane bundles and allosteric modulators bind at the interface of GABAB1 and GABAB2 subunits.[13][14][15][16][17][18][19]





Positive Allosteric Modulators[edit]



See also[edit]


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  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. PMC 3153004. PMID 21833169.
  3. ^ Hill DR, Bowery NG (March 1981). "3H-baclofen and 3H-GABA bind to bicuculline-insensitive GABA B sites in rat brain". Nature. 290 (5802): 149–52. Bibcode:1981Natur.290..149H. doi:10.1038/290149a0. PMID 6259535. S2CID 4335907.
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  5. ^ Dzitoyeva S, Dimitrijevic N, Manev H (April 2003). "Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence". Proceedings of the National Academy of Sciences of the United States of America. 100 (9): 5485–90. Bibcode:2003PNAS..100.5485D. doi:10.1073/pnas.0830111100. PMC 154371. PMID 12692303.
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  7. ^ Dimitrijevic N, Dzitoyeva S, Satta R, Imbesi M, Yildiz S, Manev H (September 2005). "Drosophila GABA(B) receptors are involved in behavioral effects of gamma-hydroxybutyric acid (GHB)". European Journal of Pharmacology. 519 (3): 246–52. doi:10.1016/j.ejphar.2005.07.016. PMID 16129424.
  8. ^ Manev H, Dimitrijevic N (May 2004). "Drosophila model for in vivo pharmacological analgesia research". European Journal of Pharmacology. 491 (2–3): 207–8. doi:10.1016/j.ejphar.2004.03.030. PMID 15140638.
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  18. ^ Kim Y, Jeong E, Jeong JH, Kim Y, Cho Y (November 2020). "Structural Basis for Activation of the Heterodimeric GABAB Receptor". Journal of Molecular Biology. 432 (22): 5966–5984. doi:10.1016/j.jmb.2020.09.023. PMID 33058878. S2CID 222841520.
  19. ^ Shen C, Mao C, Xu C, Jin N, Zhang H, Shen DD, et al. (June 2021). "Structural basis of GABAB receptor-Gi protein coupling". Nature. 594 (7864): 594–598. Bibcode:2021Natur.594..594S. doi:10.1038/s41586-021-03507-1. PMC 8222003. PMID 33911284.
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