Gamma-hydroxybutyrate receptor or GHB receptor (GHBR), originally identified as GPR172A, is a G protein-coupled receptor

G protein-coupled receptor

G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

 that binds 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).

History

The existence of a specific GHB receptor was predicted by observing the action of GHB and related compounds that primarily act on GABA_B receptors, but also exhibit a range of effects which were found not to be produced by GABA_B activity, and so were suspected of being produced by a novel and at the time unidentified receptor target. Following the discovery of the "orphan" G-protein coupled receptor GPR172A, it was subsequently found to be the GHB receptor whose existence had been previously predicted. The rat GHB receptor was first cloned and characterised in 2003 followed by the human receptor in 2007.

Function

The function of the GHB receptor appears to be quite different from that of the GABA_B receptor. It shares no sequence homology with GABA_B, and selective agonists for the GHB receptor which are not agonists at GABA_B, or administration of mixed GHBR/GABA_B agonists along with a selective GABA_B antagonist, do not produce a sedative effect, instead causing a stimulant effect followed by convulsion

Convulsion

A convulsion is a medical condition where body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body. Because a convulsion is often a symptom of an epileptic seizure, the term convulsion is sometimes used as a synonym for seizure...

s at higher doses, thought to be mediated through increased Na⁺/K⁺ current and increased release of dopamine

Dopamine

Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 and glutamate.

Agonists

• 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...
  
  
• trans-hydroxycrotonic acid
  T-HCA
  T-HCA, or trans-4-hydroxycrotonic acid, is a drug used in scientific research. It is structurally related to GHB and binds to the GHB receptor with 4-fold higher affinity than GHB itself, but is not an agonist for the primary sedative target of GHB, the GABAB receptor, and so does not produce...
  
  
• UMB66
  UMB66
  3-Chloropropanoic acid or UMB66 is a drug used in scientific research. It is structurally related to GHB and binds to the GHB receptor, but has no affinity for GABA receptors. It is also an active ingredient in some herbicide blends...
  
  
• UMB68
• UMB72
• UMB86
• (R)-3-Hydroxycyclopent-1-enecarboxylic acid
• NCS-356: 4-(4-Chlorophenyl)-4-hydroxy-but-2-enoic acid, CAS# 430440-66-7
• NCS-435: 4-(p-Methoxybenzyl)-GHB
• 4-(p-Chlorobenzyl)-GHB