GABAB receptor

protein
Name= gamma-aminobutyric acid (GABA) B receptor, 1
caption=


width=
HGNCid=4070
Symbol=GABBR1
AltSymbols=
EntrezGene=2550
OMIM=603540
RefSeq=NM_021905
UniProt=Q9UBS5
PDB=
ECnumber=
Chromosome=6
Arm=p
Band=21.3
LocusSupplementaryData=protein
Name= gamma-aminobutyric acid (GABA) B receptor, 2
caption=


width=
HGNCid=4507
Symbol=GABBR2
AltSymbols=GPR51
EntrezGene=9568
OMIM=607340
RefSeq=NM_005458
UniProt=O75899
PDB=
ECnumber=
Chromosome=9
Arm=q
Band=22.1
LocusSupplementaryData=-22.3

GABA_B receptors (GABA_BR) are metabotropic transmembrane receptors for gamma-aminobutyric acid (GABA) that are linked via G-proteins to potassium channels.cite journal |author=Chen K, Li H, Ye N, Zhang J, Wang J |title=Role of GABAB receptors in GABA and baclofen-induced inhibition of adult rat cerebellar interpositus nucleus neurons in vitro |journal=Brain Res Bull |volume=67 |issue=4 |pages=310–8 |year=2005 |pmid=16182939 |doi=10.1016/j.brainresbull.2005.07.004] These receptors are found in the central and peripheral autonomic nervous system.Martin I.L., and Dunn S.M.J. 2002. [http://www.tocris.com/pdfs/gabarev.pdf GABA receptors] Tocris Cookson Ltd. ]

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 GABA_B receptors are considered inhibitory receptors.

GABA_B receptors can also reduce the activity of adenylyl cyclase and decrease the cell’s conductance to Ca²⁺. ]

GABA_B receptors are involved in behavioral actions of ethanol, [cite journal |author=Dzitoyeva S, Dimitrijevic N, Manev H |title=Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence |journal=Proc Natl Acad Sci U S A |volume=100 |issue=9 |pages=5485–90 |year=2003 |pmid=12692303 |doi=10.1073/pnas.0830111100] gamma-Hydroxybutyric acid (GHB), [cite journal |author=Dimitrijevic N, Dzitoyeva S, Satta R, Imbesi M, Yildiz S, Manev H |title=Drosophila GABA(B) receptors are involved in behavioral effects of gamma-hydroxybutyric acid (GHB) |journal=Eur J Pharmacol |volume=519 |issue=3 |pages=246–52 |year=2005 |pmid=16129424 |doi=10.1016/j.ejphar.2005.07.016] and possibly in pain. [cite journal |author=Manev H, Dimitrijevic N |title=Drosophila model for in vivo pharmacological analgesia research |journal=Eur J Pharmacol |volume=491 |issue=2-3 |pages=207–8 |year=2004 |pmid=15140638 |doi=10.1016/j.ejphar.2004.03.030] Recent research suggests that these receptors may play an important developmental role. [cite journal |author=Dzitoyeva S, Gutnov A, Imbesi M, Dimitrijevic N, Manev H |title=Developmental role of GABAB(1) receptors in Drosophila |journal=Brain Res Dev Brain Res |volume=158 |issue=1-2 |pages=111–4 |year=2005 |pmid=16054235 |doi=10.1016/j.devbrainres.2005.06.005]

Structure

GABA_BRs are similar in structure to and in the same receptor family with metabotropic glutamate receptors.MRC (Medical Research Council). 2003. [http://www.bris.ac.uk/Depts/Synaptic/info/glutamate.html Glutamate receptors: Structures and functions.] University of Brisotol Centre for Synaptic Plasticity.] There are two subtypes of the receptor, GABA_B1 and GABA_B2, [Purves D., Augustine G.J., Fitzpatrick D., Katz L.C., LaMantia A.S., McNamara J.O., and Williams S.M. 2001. [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=neurosci.chapter.469 "Neuroscience", Second Edition.] Sinauer Associates, Inc.] ] and these appear to assemble as heterodimers in neuronal membranes by linking up by their intracellular C termini. ] ]

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

Agonists and antagonists

Baclofen is a GABA analogue which acts as a selective agonist of GABA_B receptors, and is used as a muscle relaxant. However, it can aggravate absence seizures, and so is not used in epilepsy.

Saclofen, phaclofen and SCH-50911 are selective GABA_B antagonists.

See also

* GABA receptor
* GABA_A receptor
* GABA_C receptor

References

External links

* [http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1276 IUPHAR GPCR Database - GABA_B Receptors]