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.
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> ñ subunits.
GABA<sub>B</sub> 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.
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. In the mammalian brain, two predominant, differentially expressed isoforms of the GABA<sub>B1</sub> are transcribed from the Gabbr1 gene, GABA<sub>B(1a)</sub> and GABA<sub>B(1b)</sub>, 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<sub>B</sub> 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<sub>B1</sub> and GABA<sub>B2</sub> subunits.