Gamma-hydroxybutyrate receptor (GHB receptor)

The Gamma-hydroxybutyrate (GHB) receptor, also known as GPR172A and SLC52A2, is an excitatory G protein-coupled receptor. It functions as a receptor for the neurotransmitter/drug GHB and also acts as a transporter for riboflavin. The receptor structure, based on Alphafold 2 models, contains 11 transmembrane helices and an intrinsically disordered region. It is involved in central nervous system neurotransmission, excitatory signaling via glutamate elevation, and potentially regulation of sleep, mood, and anxiety. The receptor exhibits high affinity binding for GHB, distinct from GABAB receptors, showing specific, competitive, saturable, pH-dependent, protein concentration-dependent, and brain region-dependent binding. It is thought to be metabotropic, potentially stimulating cGMP and inositol phosphate production and modulating K+ channels downstream of signaling. Ligand binding can stimulate dopamine release (biphasic at low concentrations) and may affect tryptophan transport and serotonin turnover. Historically, the receptor's existence was predicted due to non-GABAB effects of GHB. It was cloned and characterized in the early 2000s, with different discoveries identifying it as a GPCR (GPCR41, GPR172A), a retrovirus receptor, the GHB receptor, and a riboflavin transporter (SLC52A2). The GHB receptor is a therapeutic target for GHB itself (used clinically for alcoholism and narcolepsy) and interacts with compounds like NCS-382 and certain benzamide antipsychotics (amisulpride, nemonapride). It is distinct from GABAA and GABAB receptors, showing different developmental expression patterns.

Other names

GPR172AGPCR41GHBh1SLC52A2BVVLS2PAR1RFT3RFVT2hRFT3

When GHB binds, it stimulates dopamine release (biphasic at low concentrations), may trigger G protein signaling, can induce K+ channel modulation (86Rb+ efflux), and may increase tryptophan transport and serotonin turnover. It is thought to be metabotropic, potentially stimulating cGMP and inositol phosphate production and modulating K+ channels.