Contents

GABA_B receptor

GABA_B receptors (GABA_BR) are G-protein coupled receptors for gamma-aminobutyric acid (GABA), therefore making them metabotropic receptors, that are linked via G-proteinstopotassium channels.^[1] The changing potassium concentrations hyperpolarize the cell at the end of an action potential. The reversal potential of the GABA_B-mediated IPSP (inhibitory postsynaptic potential) is −100 mV, which is much more hyperpolarized than the GABA_A IPSP. GABA_B 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]

Functions[edit]

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 inhibitory receptors.

GABA_B receptors also 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]

Structure[edit]

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[edit]

Agonists[edit]

• 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

Positive Allosteric Modulators[edit]

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

Antagonists[edit]

• 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[edit]

• GABA receptor
• GABA_A receptor

References[edit]

External links[edit]