GABAB receptor

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. 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.

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

GABA_B 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.

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.

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

• ADX71441
• ASP-8062
• CGP-7930
• BHFF
• Fendiline
• BHF-177
• BSPP
• GS-39783
• INDV-1000

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