Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2003 Sep;17(12):1691-3.
doi: 10.1096/fj.02-0846fje. Epub 2003 Jul 18.

Cloning and Characterization of a Rat Brain Receptor That Binds the Endogenous Neuromodulator Gamma-Hydroxybutyrate (GHB)

Affiliations

Cloning and Characterization of a Rat Brain Receptor That Binds the Endogenous Neuromodulator Gamma-Hydroxybutyrate (GHB)

Christian Andriamampandry et al. FASEB J. .

Abstract

Gamma-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 GABA(B) receptors. Its mRNA is restricted to the brain and is particularly abundant in the hippocampus, cortex, striatum, thalamus, olfactory bulbs, and cerebellum, matching the distribution of GHB binding sites in rat brain. Southern blot revealed the presence of homologous sequences in several species including the human. Binding assays on transfected CHO cells showed a dissociation constant (Kd) of 426 nM for GHB and no affinity for GABA, baclofen, or glutamate. In patch-clamp experiments, transfected CHO cells revealed a functional G-protein-coupled receptor as demonstrated by GTP-gamma-S-induced irreversible activation. Application of 0.1-15 microM GHB specifically induced an inward current at negative membrane potentials that was not reproduced by application of baclofen (10 microM). CGP-55845, a GABA(B) receptor antagonist, did not inhibit the GHB-induced response nor did the GHB receptor antagonist NCS-382, suggesting that the GHB receptor system includes several subtypes.

Similar articles

See all similar articles

Cited by 24 articles

See all "Cited by" articles

LinkOut - more resources

Feedback