GABA_B receptors (GABA_BR) are

G-protein coupled receptors G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of protein family, evolution ...

for gamma-aminobutyric acid (GABA), therefore making them

metabotropic receptor A metabotropic receptor, also referred to by the broader term G-protein-coupled receptor, is a type of membrane receptor that initiates a number of metabolic steps to modulate cell activity. The nervous system utilizes two types of receptors: met ...

s, that are linked via

G-protein G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their act ...

s to

potassium channel Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cel ...

s. 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 The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

and the autonomic division of the

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...

. 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 Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity such as from a spinal cord injury or multiple sclerosis. It may also be used for hiccups and muscle spasms near the end of life. It is ta ...

Functions

GABA_BRs stimulate the opening of K⁺ channels, specifically GIRKs, which brings the

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

closer to the

equilibrium potential In a biological membrane, the reversal potential is the membrane potential at which the direction of ionic current reverses. At the reversal potential, there is no net flow of ions from one side of the membrane to the other. For channels that are pe ...

of K⁺. This reduces the frequency of

action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

s which reduces

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

release. Thus GABA_B receptors are inhibitory receptors. GABA_B receptors also reduces the activity of

adenylyl cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...

and Ca²⁺ channels by using G-proteins with G_i/G₀ α subunits. GABA_B receptors are involved in behavioral actions of

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

gamma-hydroxybutyric acid ''gamma''-Hydroxybutyric acid (or γ-hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic acid) is a naturally occurring neurotransmitter and a depressant drug. It is a precursor to GABA, glutamate, and glycine in certain brain areas. ...

(GHB), and possibly in pain. Recent research suggests that these receptors may play an important developmental role. 6VJM GABAB Receptor dimer inactive

Structure

GABA_B Receptors are similar in structure to and in the same receptor family with

metabotropic glutamate receptor The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate rece ...

s.MRC (Medical Research Council). 2003.
Glutamate receptors: Structures and functions.
University of Brisotol Centre for Synaptic Plasticity. There are two subunits of the receptor, GABA_B1 and GABA_B2, and these appear to assemble as

heterodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

s in neuronal membranes by linking up by their intracellular C termini. In the mammalian brain, two predominant, differentially expressed

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...

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 Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample s ...

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 Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity such as from a spinal cord injury or multiple sclerosis. It may also be used for hiccups and muscle spasms near the end of life. It is ta ...

is a GABA analogue which acts as a selective agonist of GABA_B receptors, and is used as a

muscle relaxant A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeu ...

. However, it can aggravate

absence seizure Absence seizures are one of several kinds of generalized seizures. These seizures are sometimes referred to as petit mal seizures (from the French for "little illness", a term dated in the late 18th century). Absence seizures are characterized by ...

s, and so is not used in

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...

. * ''gamma''-Hydroxybutyrate (GHB) * Phenibut * 4-Fluorophenibut * Isovaline * 3-Aminopropylphosphinic acid * Lesogaberan *

SKF-97541 SKF-97,541 is a compound used in scientific research which acts primarily as a selective GABAB receptor agonist. It has sedative effects in animal studies and is widely used in research into potential treatment of various types of drug addicti ...

: 3-Aminopropyl(methyl)phosphinic acid, 10x more potent than baclofen as GABA_B agonist, but also GABA_A-rho antagonist * CGP-44532

Positive Allosteric Modulators

CGP-7930 CGP-7930 is a compound used in scientific research which acts as a positive allosteric modulator at the GABAB receptor. It has anxiolytic effects in animal studies, and has a synergistic effect with GABAB agonists such as baclofen and GHB, as w ...

* BHFF *

Fendiline Fendiline is a '' nonselective'' calcium channel blocker. References Calcium channel blockers Amines {{cardiovascular-drug-stub ...

* BHF-177 *

BSPP BSPP may refer to: * BSPP (drug) * British Society for Plant Pathology * Burma Socialist Programme Party * Paris Fire Brigade The Paris Fire Brigade (french: Brigade des sapeurs-pompiers de Paris, BSPP) is a French Army unit which serves as t ...

* GS-39783

Antagonists

Homotaurine Homotaurine (also known as tramiprosate ( INN), 3-amino-1-propanesulfonic acid, or 3-APS) is a natural sulfonic acid found in seaweed. It is analogous to taurine, but with an extra carbon in its chain. It has GABAergic activity, apparently by mim ...

Ginsenosides Ginsenosides or panaxosides are a class of natural product steroid glycosides and triterpene saponins. Compounds in this family are found almost exclusively in the plant genus ''Panax'' (ginseng), which has a long history of use in traditional ...

* 2-OH-saclofen * Saclofen * Phaclofen *

SCH-50911 SCH-50911 is a selective GABAB antagonist. Its main applications are in pharmacology research. SCH-50911 also acts as an anticonvulsant under normal conditions. SCH-50911 induces acute withdrawal syndrome in GHB-dependent rats, similar to the de ...

* 2-Phenethylamine *

CGP-35348 CGP-35348 is a compound used in scientific research which acts as an antagonist at GABAB receptors. CGP-35348 was ineffective up to 100 μM to antagonize the inhibitory release of GABA elicited by baclofen, doing it selective as GABAB heterore ...

* CGP-52432: 3-( 3,4-Dichlorophenyl)methylmino]propyl) diethoxymethyl)phosphinic acid, CAS# 139667-74-6 * CGP-55845: (2S)-3-( 1S)-1-(3,4-Dichlorophenyl)ethylmino-2-hydroxypropyl)(phenylmethyl)phosphinic acid, CAS# 149184-22-5 * SGS-742

References

External links

{{G protein-coupled receptors, g3 G protein-coupled receptors GABA