GABAB receptor

gamma-aminobutyric acid (GABA) B receptor, 1
Identifiers
Symbol	GABBR1
NCBI gene	2550
HGNC	4070
OMIM	603540
RefSeq	NM_021905
UniProt	Q9UBS5
Other data
Locus	Chr. 6 p21.3
Search for Structures Swiss-model Domains InterPro

gamma-aminobutyric acid (GABA) B receptor, 2
Identifiers
Symbol	GABBR2
Alt. symbols	GPR51
NCBI gene	9568
HGNC	4507
OMIM	607340
RefSeq	NM_005458
UniProt	O75899
Other data
Locus	Chr. 9 q22.1-22.3
Search for Structures Swiss-model Domains InterPro

GABA_B receptors (GABA_BR) are G-protein coupled receptors for gamma-aminobutyric acid (GABA). GABA_B receptors are found in the central nervous system and the autonomic division of the peripheral nervous system. ^[1]

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]

Functions

GABA_BRs 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 GABA_B receptors are usually considered as inhibitory receptors.

GABA_B receptors can also function as an excitatory receptor and facilitate neurotransmitter release via increasing the activity of Ca_V2.3 channels. ^[3]

GABA_B receptors usually reduces the activity of adenylyl cyclase and Ca²⁺ channels by using G-proteins with G_i/G₀ α subunits. ^[4]

GABA_B 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

Structure

GABA_B receptors are similar in structure to and in the same receptor family with metabotropic glutamate receptors. ^[10] There are two subunits of the receptor, GABA_B1 and GABA_B2, ^[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 GABA_B1 are transcribed from the Gabbr1 gene, GABA_B(1a) and GABA_B(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 GABA_B 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 GABA_B1 and GABA_B2 subunits. ^{[13] [14] [15] [16] [17] [18] [19]}

Ligands

GABA

GHB

Lesogaberan

Agonists

• GABA
• 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.
• gamma-Hydroxybutyrate (GHB)
• Phenibut
• 4-Fluorophenibut
• Isovaline
• 3-Aminopropylphosphinic acid
• Lesogaberan
• SKF-97541: 3-Aminopropyl(methyl)phosphinic acid, 10× more potent than baclofen as GABA_B agonist, but also GABA_A-ρ antagonist
• Taurine
• CGP-44532

CGP-7930

Positive allosteric modulators

• CGP-7930 ^{[20] [21]}
• BHFF
• Fendiline
• BHF-177 ^[22]
• BSPP
• GS-39783 ^[23]

Phaclofen

SCH-50911

Antagonists

• Homotaurine ^[24]
• Ginsenosides ^[25]
• 2-OH-saclofen
• 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 ^{[26] [27]}

See also

• GABA receptor
• GABA_A receptor

References

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