A High‐Affinity, Na⁺‐Dependent Uptake System for γ‐Hydroxybutyrate in Membrane Vesicles Prepared from Rat Brain

Abstract

gamma-Hydroxybutyrate (GHB) is a compared with numerous neuropharmacological properties. The discovery of its biosynthetic system, together with its endogenous repartition, have prompted its possible implication in neurotransmission. The role is also supported by the existence, reported here, of a high-affinity uptake system for GHB (Km = 46.4 microM) in both purified brain plasma membrane vesicles and in the crude mitochondrial fraction. GHB uptake is dependent on a Na+ gradient but is independent of the membrane electrical potential. Cl- and K+ can also modulate the uptake. As an approach to determine the conformation required for GHB uptake, a series of related compounds, including aryl- or alkyl- derivatives, has been examined for ability to inhibit GHB uptake. The regional distribution of uptake is also indicative of its possible physiological role, since in striatum, an area where GHB has a known pharmacological effect on dopaminergic neurons, this uptake activity is the highest.

Overview of the Proton-coupled MCT (SLC16A) Family of Transporters: Characterization, Function and Role in the Transport of the Drug of Abuse γ-Hydroxybutyric Acid

“…Additional studies have demonstrated that GHB transport occurs via a carrier-mediated processes in the intestine (91), brain (95), and at the blood-brain barrier (5). MCT expression has been demonstrated along the length of the intestine with MCT1 being the predominant isoform (19).…”

Brain Uptake of the Drug of Abuse γ-Hydroxybutyric Acid in Rats

“…SMCT1 is expressed on neurons and may result in increased intracellular GHB concentrations (Martin et al, 2006). In addition, GABA inhibits the uptake of GHB into synaptosomes (Benavides et al, 1982), suggesting that another transporter (potentially one of the GAT family) is involved in the cellular uptake of GHB. Additional investigation is necessary to characterize the uptake of GHB by astrocytes and neurons, and to determine the involvement of other transporters such as neuronal SMCTs or those of the GAT family in the brain distribution of GHB.…”

The Role of Monocarboxylate Transporter 2 and 4 in the Transport of γ-Hydroxybutyric Acid in Mammalian Cells

“…The transport of GHB across various biological barriers and cellular membranes, such as blood-brain barrier, brain cells, and proximal tubule cells, requires specific transporters (Benavides et al, 1982;Bhattacharya and Boje, 2004;Wang et al, 2006a). The renal transport of GHB has been studied previously, and MCT1 represents an important transporter for GHB transport across the proximal tubule cells (Wang et al, 2006a).…”