Cloning and characterization of a rat brain receptor that binds the endogenous neuromodulator γ‐hydroxybutyrate

  title={Cloning and characterization of a rat brain receptor that binds the endogenous neuromodulator $\gamma$‐hydroxybutyrate},
  author={Christian Andriamampandry and Omar Taleb and Sandrine Viry and Claude Muller and J P Humbert and Serge Gobaille and Dominique Aunis and Michel Maitre},
  journal={The FASEB Journal},
γ‐Hydroxybutyrate (GHB) is an endogenous neuromodulator with therapeutical applications in anesthesia, sleep disorders, and drug addiction. We report the cloning of a GHB receptor from a rat hippocampal cDNA library. This receptor has a molecular mass of 56 kDa and belongs to the seven‐transmembrane receptor family. The peptidic sequence has no significant homology with any known receptor, including GABAB receptors. Its mRNA is restricted to the brain and is particularly abundant in the… 

Immunohistochemical localization of a GHB receptor‐like protein isolated from rat brain

Investigation of the regional and cellular distribution of this receptor in rat brain selected several specific peptides belonging to the extracellular domains of the receptor to be used as specific immunogens to raise polyclonal antibodies in the rabbit and showed receptor protein distribution closely resembling the distribution of GHB high‐affinity binding sites.

γ-Hydroxybutyric Acid (GHB) Is Not an Agonist of Extrasynaptic GABAA Receptors

The results suggest either that GHB is not a high affinity agonist at native α4β1δ receptors, or that these receptors do not exist in classical areas associated with extrasynaptic currents.

A single acute pharmacological dose of γ-hydroxybutyrate modifies multiple gene expression patterns in rat hippocampus and frontal cortex.

It is demonstrated that a single acute anesthetic dose of 1 g/kg GHB alters a large number of genes, 121 in hippocampus and 53 in prefrontal cortex; 16 genes were modified simultaneously in both brain regions by using DNA microarray studies.

GHB receptor targets in the CNS: focus on high-affinity binding sites.

A Review of Pharmacology of NCS‐382, a Putative Antagonist of γ‐Hydroxybutyric Acid (GHB) Receptor

It is concluded that NCS-382 is a good ligand but not a selective antagonist for GHB receptor, capable of either eliciting qualitatively similar effects to those of GHB or enhancing some actions ofGHB.

Gamma-hydroxybutyric acid: neurobiology and toxicology of a recreational drug.

Investigation of the inborn error of metabolism succinic semialdehyde deficiency and the murine model of this disorder (SSADH knockout mice), in which GHB plays a major role, may help dissect out GHB- and GABA(B) receptor-mediated mechanisms.



Structure and functional expression of cloned rat serotonin 5HT‐2 receptor.

A complementary DNA (cDNA) encoding a serotonin receptor with 51% sequence identity to the 5HT‐1C subtype was isolated from a rat brain cDNA library by homology screening. Transient expression of the

Evidence for a G Protein‐Coupled γ‐Hydroxybutyric Acid Receptor

The hypothesis that GHB induces a Gprotein‐mediated decrease in adenylyl cyclase via a GHB‐specific G protein‐coupled presynaptic receptor that is different from the GABABR is supported.

Gamma-hydroxybutyric acid binding sites in rat and human brain synaptosomal membranes.

Evidence for a G protein-coupled gamma-hydroxybutyric acid receptor.

  • O. Snead
  • Biology, Psychology
    Journal of neurochemistry
  • 2000
The hypothesis that GHB induces a Gprotein-mediated decrease in adenylyl cyclase via a GHB-specific G protein-coupled presynaptic receptor that is different from the GABA(B)R was tested and supported.


High affinity binding site for γ-hydroxybutyric acid in rat brain

A specific gamma-hydroxybutyrate receptor ligand possesses both antagonistic and anticonvulsant properties.

The results suggest that NCS-382 may represent a harbinger for a new class of anticonvulsant drugs that most probably act by modifying the endogenous GHB system.

Cloning of a rat brain succinic semialdehyde reductase involved in the synthesis of the neuromodulator gamma-hydroxybutyrate.

The recombinant enzyme showed catalytic properties similar to those of the SSR purified from rat brain, particularly in regard to its substrate affinities and Ki for inhibition by phthalaldehydic acid.

Regional differences in depolarization-induced release of γ-hydroxybutyrate from rat brain slices