GABA B receptor
Encyclopedia
GABAB receptors are metabotropic transmembrane receptors for gamma-aminobutyric acid
(GABA) that are linked via G-proteins to potassium
channels. These receptors are found in the central and peripheral autonomic nervous system
.
which brings the neuron
closer to the equilibrium potential
of K+, hyperpolarising
the neuron. This prevents sodium channels from opening, action potential
s from firing, and VDCCs
from opening, and so stops neurotransmitter
release. Thus GABAB receptors are considered inhibitory receptors.
GABAB receptors can also reduce the activity of adenylyl cyclase and decrease the cell
’s conductance
to Ca2+.
GABAB 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.
s. There are two subtypes of the receptor, GABAB1
and GABAB2
, and these appear to assemble as heterodimers in neuronal membranes by linking up by their intracellular C termini.
It is speculated that binding of GABA causes the subunits to swing shut around the agonist like a venus fly trap.
Gamma-aminobutyric acid
γ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
(GABA) that are linked via G-proteins to potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
channels. These receptors are found in the central and peripheral autonomic nervous system
Autonomic nervous system
The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
.
Functions
They can stimulate the opening of K+ channelsIon channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
which brings the neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
closer to the equilibrium potential
Reversal potential
In a biological membrane, the reversal potential of an ion is the membrane potential at which there is no net flow of that particular ion from one side of the membrane to the other...
of K+, hyperpolarising
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
the neuron. This prevents sodium channels from opening, action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
s from firing, and VDCCs
Voltage-dependent calcium channel
Voltage-dependent calcium channels are a group of voltage-gated ion channels found in excitable cells with a permeability to the ion Ca2+...
from opening, and so stops neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
release. Thus GABAB receptors are considered inhibitory receptors.
GABAB receptors can also reduce the activity of adenylyl cyclase and decrease the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
’s conductance
Conductance
Conductance may refer to:* Electrical conductance, the ability for electricity to flow a certain path* Fluid conductance, the ability for fluid to transmit through materials* Thermal conductivity, the ability for temperatures to transmit through materials...
to Ca2+.
GABAB receptors are involved in behavioral actions of ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
, gamma-Hydroxybutyric acid
Gamma-Hydroxybutyric acid
γ-Hydroxybutyric acid , also known as 4-hydroxybutanoic acid and sodium oxybate when used for medicinal purposes, is a naturally occurring substance found in the central nervous system, wine, beef, small citrus fruits, and almost all animals in small amounts. It is also categorized as an illegal...
(GHB), and possibly in pain. Recent research suggests that these receptors may play an important developmental role.
Structure
GABABRs are similar in structure to and in the same receptor family with metabotropic glutamate receptorMetabotropic 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...
s. There are two subtypes of the receptor, GABAB1
GABBR1
Gamma-aminobutyric acid B receptor, 1 , is a G-protein coupled receptor subunit encoded by the GABBR1 gene.-Interactions:GABBR1 has been shown to interact with ATF4 and GABBR2.-Further reading:...
and GABAB2
GABBR2
Gamma-aminobutyric acid B receptor, 2 is a G-protein coupled receptor subunit encoded by the GABBR2 gene in humans.-Further reading:...
, and these appear to assemble as heterodimers in neuronal membranes by linking up by their intracellular C termini.
It is speculated that binding of GABA causes the subunits to swing shut around the agonist like a venus fly trap.
Selective Ligands
Agonists
- GABAGamma-aminobutyric acidγ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
- BaclofenBaclofenBaclofen is a derivative of gamma-aminobutyric acid . It is primarily used to treat spasticity and is under investigation for the treatment of alcoholism....
is a GABA analogueAnalog (chemistry)In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
which acts as a selective agonist of GABAB receptors, and is used as a muscle relaxantMuscle relaxantA muscle relaxant is a drug which 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 therapeutic groups: neuromuscular blockers and spasmolytics...
. However, it can aggravate absence seizureAbsence seizureAbsence seizures are one of several kinds of seizures. These seizures are sometimes referred to as petit mal seizures ....
s, and so is not used in epilepsyEpilepsyEpilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
. - gamma-Hydroxybutyrate (GHB)
- PhenibutPhenibutβ-Phenyl-γ-aminobutyric acid, better known as phenibut or less commonly fenibut or phenybut, is a derivative of the naturally occurring inhibitory neurotransmitter γ-aminobutyric acid . The addition of a phenyl ring allows phenibut to cross the blood brain barrier...
- 3-Aminopropylphosphinic acid
- LesogaberanLesogaberanLesogaberan is an experimental drug candidate under development by AstraZeneca for the treatment of gastroesophageal reflux disease . As a GABAB receptor agonist, it has the same mechanism of action as baclofen, but is anticipated to have fewer of the central nervous system side effects that...
- SKF-97541SKF-97541SKF-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 addiction....
: 3-Aminopropyl(methyl)phosphinic acid, 10x more potent than baclofen as GABAB agonist, but also GABAC antagonist - CGP-44532
Positive Allosteric Modulators
- CGP-7930CGP-7930CGP-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 well as reducing self-administration of ethanol and...
- BHFFBHFFBHFF 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 good oral bioavailability....
- BHF-177BHF-177BHF-177 is a compound used in scientific research which acts as a positive allosteric modulator at the GABAB receptor. It was shown to reduce self-administration of nicotine in animal studies....
- BSPPBSPP (drug)BSPP is a compound used in scientific research which acts as a positive allosteric modulator at the GABAB receptor. It has a synergistic effect with GABAB agonists such as baclofen at GABAB autoreceptors but not heteroreceptors, suggesting it may be useful for distinguishing between these GABAB...
- GS-39783GS-39783GS-39783 is a compound used in scientific research which acts as a positive allosteric modulator at the GABAB receptor. It has been shown to produce anxiolytic effects in animal studies, and reduces self-administration of ethanol , cocaine and nicotine....
Antagonists
- SaclofenSaclofenSaclofen is a competitive antagonist for the GABAB receptor. This drug is an analogue of the GABAB agonist Baclofen. The GABAB receptor is heptahelical receptor, expressed as an obligate heterodimer, which couples to the Gi/o class of heterotrimeric G-proteins...
- PhaclofenPhaclofenPhaclofen, or phosphonobaclofen, is a selective antagonist for the GABAB receptor....
- SCH-50911SCH-50911SCH-50911 is a selective GABAB antagonist developed by Schering-Plough Corporation. Its main applications are in pharmacology research, but it has been found to quickly and effectively reverse the symptoms of GHB overdose in mice. In one experiment, mice were given a lethal dose of GHB followed...
- CGP-35348CGP-35348CGP-35348 is a compound used in scientific research which acts as an antagonist at GABAB receptors....
- 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 receptorGABA receptorThe GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid , the chief inhibitory neurotransmitter in the vertebrate central nervous system...
- GABAA receptorGABA A receptorThe GABAA receptor is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid , the major inhibitory neurotransmitter in the central nervous system. Upon activation, the GABAA receptor selectively conducts Cl- through its pore, resulting in...
- GABAA-ρ receptor