γ-Hydroxybutyric acid (GHB) and γ-aminobutyric acidB receptor (GABABR) binding sites are distinctive from one another: molecular evidence

@article{Wu2004HydroxybutyricA,
  title={$\gamma$-Hydroxybutyric acid (GHB) and $\gamma$-aminobutyric acidB receptor (GABABR) binding sites are distinctive from one another: molecular evidence},
  author={Ying Wu and Saima Ali and Gholamreza Ahmadian and Chun Che Liu and Yu Tian Wang and Kenneth Michael Gibson and Andrew R. Calver and Joseph Francis and Menelas N. Pangalos and O. Carter Snead},
  journal={Neuropharmacology},
  year={2004},
  volume={47},
  pages={1146-1156}
}
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54 Citations
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54 Citations

Novel Cyclic γ-Hydroxybutyrate (GHB) Analogs with High Affinity and Stereoselectivity of Binding to GHB Sites in Rat Brain

Three conformationally restricted GHB analogs are synthesized and assayed for binding against the GHB-specific ligand [3H]NCS-382 in rat brain homogenate and show excellent potential as lead structures and novel tools for studying specific GHB receptor-mediated pharmacology.

γ-Hydroxybutyric Acid

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 GABAB receptor-mediated mechanisms.

Novel Radioiodinated γ-Hydroxybutyric Acid Analogues for Radiolabeling and Photolinking of High-Affinity γ-Hydroxybutyric Acid Binding Sites

A 125I-labeled photoaffinity derivative of the new GHB ligand is developed and is a useful tool for in vitro studies of the specific high-affinity GHB binding sites and can be used as a probe for isolation of the elusiveGHB binding protein.

Unravelling the brain targets of γ-hydroxybutyric acid

γ-Hydroxybutyrate (GHB) induces GABAB receptor independent intracellular Ca2+ transients in astrocytes, but has no effect on GHB or GABAB receptors of medium spiny neurons in the nucleus accumbens

Drosophila GABAB receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB)

Phenylacetic acids and the structurally related non‐steroidal anti‐inflammatory drug diclofenac bind to specific γ‐hydroxybutyric acid sites in rat brain

Measuring the affinities of structurally related NSAIDs for the [3H]NCS‐382 site identified diclofenac, a clinically relevant NSAID of the phenylacetic acid (PAA) type, as a GHB ligand (Ki value of 5.1 μm), and other non‐NSAID PAAs also exhibited affinity similar to GHB.

Metabolic GHB precursor succinate binds to γ‐hydroxybutyrate receptors: Characterization of human basal ganglia areas nucleus accumbens and globus pallidus

It is suggested that succinate (and possibly drugs available as succinate salt derivatives) can mimic some of the actions of GHB.

Succinic Semialdehyde Dehydrogenase Deficiency: GABAB receptor-mediated function

Gamma-hydroxybutyrate abuse and dependence

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References

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Relation of the [3H]γ-hydroxybutyric acid (ghb) binding site to the γ-aminobutyric acidb (gabab) receptor in rat brain

Stereoselectivity of NCS-382 binding to γ-hydroxybutyrate receptor in the rat brain

Specific γ‐hydroxybutyrate‐binding sites but loss of pharmacological effects of γ‐hydroxybutyrate in GABAB(1)‐deficient mice

It appears that all studied GHB effects are GABAB receptor dependent, and the GHB‐induced GTPγ[35S] responses are mediated by GABAB receptors.

Binding characteristics of the gamma-hydroxybutyric acid receptor antagonist [(3)H](2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid in the rat brain.

Radioligand binding studies with [(3)H](2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid ([(3)H]NCS-382), an antagonist of gamma-hydroxybutyric acid (GHB) receptor,…

γ-Hydroxybutyrate is a weak agonist at recombinant GABAB receptors

In vivo conversion of γ-aminobutyric acid and 1,4-butanediol to γ-hydroxybutyric acid in rat brain

The ontogeny of [3H]γ-hydroxybutyrate and [3H]GABA B binding sites: relation to the development of experimental absence seizures

gamma-Hydroxybutyrate conversion into GABA induces displacement of GABAB binding that is blocked by valproate and ethosuximide.

It is demonstrated that the inhibition of GHB's conversion into GABA by rat brain membranes blocks the ability ofGHB to interfere with GABAB binding, which could explain the misinterpretation of in vitro or in vivo experiments where GHB possesses a GABA-like effect.

Quantitative autoradiographic analysis of the new radioligand [3H](2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid ([3H]NCS-382) at γ-hydroxybutyric acid (GHB) binding sites in rat brain

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.