GABA receptor

The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABA_A and GABA_B.

GABA_A receptors are ligand-gated ion channels (also known as ionotropic receptors), whereas GABA_B receptors are G protein-coupled receptors (also known as metabotropic receptors).

Ligand-gated ion channels: GABA_A

It has long been recognized that the fast response of neurons to GABA that is blocked by bicuculline and picrotoxin is due to direct activation of an anion channel. This channel was subsequently termed the GABA_A receptor. Fast-responding GABA receptors are members of family of Cys-loop ligand-gated ion channels. Members of this superfamily, which includes nicotinic acetylcholine receptors, GABA_A receptors, glycine and 5-HT₃ receptors, possess a characteristic loop formed by a disulfide bond between two cysteine residues.

In ionotropic GABA_A receptors, binding of GABA molecules to their binding sites in the extracellular part of the receptor triggers opening of a chloride ion-selective pore. The increased chloride conductance drives the membrane potential towards the reversal potential of the Cl¯ ion which is about –65 mV in neurons, inhibiting the firing of new action potentials. This mechanism is responsible for the sedative effects of GABA_A allosteric agonists.

Agonist

An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response. Whereas an agonist causes an action, an antagonist blocks the action of the agonist and an inverse agonist causes an action opposite to that of the agonist.

Types of agonists

Receptors can be activated by either endogenous (such as hormones and neurotransmitters) or exogenous (such as drugs) agonists, resulting in a biological response. A physiological agonist is a substance that creates the same bodily responses but does not bind to the same receptor.

An endogenous agonist for a particular receptor is a compound naturally produced by the body that binds to and activates that receptor. For example, the endogenous agonist for serotonin receptors is serotonin, and the endogenous agonist for dopamine receptors is dopamine.

A superagonist is a compound that is capable of producing a greater maximal response than the endogenous agonist for the target receptor, and thus has an efficacy of more than 100%. This does not necessarily mean that it is more potent than the endogenous agonist, but is rather a comparison of the maximum possible response that can be produced inside the cell following receptor binding.

Alpha-2 adrenergic receptor

The alpha-2 (α₂) adrenergic receptor (or adrenoceptor) is a G protein-coupled receptor (GPCR) associated with the G_i heterotrimeric G-protein. It consists of three highly homologous subtypes, including α_2A-, α_2B-, and α_2C-adrenergic. Some species other than humans express a fourth α_2D-adrenergic receptor as well.Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α₂-adrenergic receptor in the central and peripheral nervous systems.

Cellular localisation

α_2A adrenergic receptor is localised in the following central nervous system (CNS) structures:

Whereas the α_2B adrenergic receptor is localised in the following CNS structures:

and the α_2C adrenergic receptor is localised in the CNS structures:

GABA receptor agonist

A GABA receptor agonist is a drug that is an agonist for one or more of the GABA receptors, producing typically sedative effects, and may also cause other effects such as anxiolytic, anticonvulsant, and muscle relaxant effects. There are three receptors of the gamma-aminobutyric acid. The two receptors GABA-α and GABA-ρ are ion channels that signal chloride and diminish further action potentials. The GABA-β receptor belongs to the class of G-Protein coupled receptors that inhibit adenylyl cyclase, therefore leading to decreased cyclic adenosine monophosphate (cAMP). GABA-α and GABA-ρ receptors produce sedative and hypnotic effects and have anti-convulsion properties. GABA-β receptors too produce sedative effects. Furthermore they lead to changes in gene transcription.

GABA_A receptor

Agonists

PAMs