Gamma-aminobutyric acid type B receptor (GABAB receptor) (GABABR)

The Gamma-aminobutyric acid type B receptor (GABAB receptor) is a Class C G protein-coupled receptor that functions as an obligate heterodimer composed of two subunits, GABAB1 and GABAB2 (PubMed: 9872316). It is widely distributed throughout the central nervous system and mediates slow, prolonged inhibitory neurotransmission by responding to the primary inhibitory neurotransmitter, GABA (PubMed: 10075644). The GABAB1 subunit contains the orthosteric binding site for ligands, while the GABAB2 subunit is essential for G-protein coupling and the trafficking of the heterodimer to the cell surface (PubMed: 18165688). Activation of the receptor triggers Gi/o protein signaling, which inhibits adenylyl cyclase, opens inwardly rectifying potassium channels (GIRK), and closes voltage-gated calcium channels, thereby reducing neuronal excitability and neurotransmitter release (PubMed: 10773016). This receptor is a significant therapeutic target for treating spasticity, chronic pain, and potentially neuropsychiatric conditions like anxiety and substance use disorders (PubMed: 33442842). Baclofen, a selective agonist, is clinically used to manage muscle spasticity, though its use is limited by side effects such as sedation and the risk of withdrawal symptoms (StatPearls: NBK553132). Positive allosteric modulators (PAMs) are currently being explored as alternative therapies with potentially fewer side effects (PubMed: 10906333).

Other names

GABAB1–GABAB2 heterodimerGABBR1–GABBR2 complexMetabotropic GABA receptorGABAB receptorGABABR

Agonist binding to the GABAB1 subunit induces a conformational change in the GABAB2 subunit, which activates Gi/o proteins, leading to inhibition of adenylyl cyclase, activation of G protein-coupled inwardly rectifying potassium (GIRK) channels, and inhibition of voltage-gated calcium channels.