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

SPECIFIC AIMSγ-Hydroxybutyrate (GHB) is a putative neuromodulator of the mammalian brain that derives from GABA via transamination and subsequent reduction through a specific succinic semialdehyde reductase (SSR). GHB and SSR are colocalized in some neurons and neuronal endings and GHB is accumulated in synaptic vesicles by an active transport. At micromolar concentrations, GHB exerts a specific influence on some Ca2+ and K+ conductances expressed by certain neuronal cell lines. These effects are thought to be mediated by GHB binding sites, which have specific ontogenesis, pharmacological, and kinetic properties, together with a particular distribution profile in the brain of several species. Peripherally administered GHB potentiates and adapts this endogenous GHB system and is approved in various countries for the treatment of narcolepsy, sleep disturbances, and ethanol withdrawal. GHB is also a drug of abuse for its anxiolytic, euphoric, and sedative properties. In this study, we report the cloning and ...