GABA<sub>B</sub> receptors (GABA<sub>B</sub>R) are G-protein coupled receptors for gamma-aminobutyric acid (GABA). GABA<sub>B</sub> receptors are found in the central nervous system and the autonomic division of the peripheral nervous system.

The receptors were first named in 1981 when their distribution in the CNS which was determined by Norman Bowery and his team using radioactively labelled baclofen.

Functions

GABA<sub>B</sub>Rs stimulate the opening of K<sup>+</sup> channels, specifically GIRKs, which brings the neuron closer to the equilibrium potential of K<sup>+</sup>. This reduces the frequency of action potentials which reduces neurotransmitter release. Thus GABA<sub>B</sub> receptors are usually considered as inhibitory receptors.

GABA<sub>B</sub> receptors can also function as an excitatory receptor and facilitate neurotransmitter release via increasing the activity of Ca<sub>V2.3</sub> channels.

GABA<sub>B</sub> receptors usually reduces the activity of adenylyl cyclase and Ca<sup>2+</sup> channels by using G-proteins with G<sub>i</sub>/G<sub>0</sub> α subunits.

GABA<sub>B</sub> receptors are involved in behavioral actions of ethanol, gamma-hydroxybutyric acid (GHB), baclofen, and possibly in pain. Recent research suggests that these receptors may play an important developmental role.

thumb|Receptor dimer, inactive apo state, cartoon representation

Structure

GABA<sub>B</sub> receptors are similar in structure to and in the same receptor family with metabotropic glutamate receptors. There are two subunits of the receptor, GABA<sub>B1</sub> and GABA<sub>B2</sub>, and these appear to assemble as obligate heterodimers in neuronal membranes by linking up by their intracellular C termini. This might potentially offer more complexity in terms of the function due to different composition of the receptor.

Ligands

thumb|120px|[[Gamma-aminobutyric acid|GABA]]

thumb|120px|[[gamma-Hydroxybutyrate|GHB]]

thumb|120px|[[Lesogaberan]]

Agonists

  • GABA
  • Baclofen is a GABA analogue which acts as a selective agonist of GABA<sub>B</sub> 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<sub>B</sub> agonist, but also GABA<sub>A</sub>-ρ antagonist
  • Taurine
  • CGP-44532

thumb|140px|[[CGP-7930]]

Positive allosteric modulators

  • ASP-8062
  • CGP-7930
  • BHFF
  • Fendiline
  • BHF-177
  • BSPP
  • GS-39783
  • INDV-1000

thumb|130px|[[Phaclofen]]

thumb|110px|[[SCH-50911]]

Antagonists

  • Homotaurine
  • Ginsenosides
  • 2-Hydroxysaclofen
  • 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

See also

  • GABA receptor
  • GABA<sub>A</sub> receptor

References