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}
}

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.

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.

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.

GABAB Receptor-Positive Modulators: Brain Region-Dependent Effects

The results show that GABAB receptor-positive modulators enhance [35S]GTPγS binding stimulated by GABAB receptors agonists in a brain region-dependent manner, possibly allowing for more selective therapeutic targeting of the GABAB system.

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

Succinic Semialdehyde Dehydrogenase Deficiency: GABAB receptor-mediated function

...

References

SHOWING 1-10 OF 41 REFERENCES

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,

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.

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.