# GABAB receptor

GABA$_B$ receptors (GABA$_B$R) are G-protein coupled receptors for gamma-aminobutyric acid (GABA), therefore making them metabotropic receptors, that are linked via G-proteins to potassium channels. 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.
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.

## Functions

GABA$_B$Rs 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. Thus GABA$_B$ receptors are inhibitory receptors.
GABA$_B$ receptors also reduces the activity of adenylyl cyclase and Ca$^{2+}$ channels by using G-proteins with G$_i$/G$_0$ α subunits.
GABA$_B$ receptors are involved in behavioral actions of ethanol, gamma-hydroxybutyric acid (GHB), and possibly in pain. Recent research suggests that these receptors may play an important developmental role.

## Structure

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

## Ligands
### 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

### Positive Allosteric Modulators

* CGP-7930
* BHFF
* Fendiline
* BHF-177
* BSPP
* GS-39783

### Antagonists

* Homotaurine
* Ginsenosides
* 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