Gamma-aminobutyric acid receptor type B subunit 2 (GABBR2)

Gamma-aminobutyric acid receptor type B subunit 2 (GABBR2) is a critical component of the heterodimeric GABAB receptor, a Class C G protein-coupled receptor (GPCR) that mediates slow, prolonged inhibitory neurotransmission in the central nervous system (UniProt: O75899). While the GABBR1 subunit contains the ligand-binding site for GABA, GABBR2 is essential for the proper trafficking of the heterodimer to the plasma membrane and is the primary subunit responsible for coupling with Gi/o proteins to initiate intracellular signaling (PubMed: 10773016). Activation of the GABAB receptor complex leads to the inhibition of adenylyl cyclase, the opening of potassium channels, and the closing of voltage-gated calcium channels, effectively reducing neuronal excitability (PubMed: 11595415). Dysregulation or mutations in GABBR2 are associated with various neurological conditions, including epilepsy, schizophrenia, and spasticity (NCBI Gene: 9568). Pharmacologically, GABBR2 is a target for baclofen, a muscle relaxant used to treat spasticity, and is a focus for developing positive allosteric modulators for treating addiction and cognitive disorders (PubMed: 25323711).

Other names

GPR51GABABR2G-protein coupled receptor 51GABA-B receptor 2GB2HGNC:4255

Agonist binding to the GABAB receptor complex, which exists as a heterodimer of B1 and B2 subunits, triggers G-protein signaling specifically through the B2 subunit; this leads to the inhibition of adenylyl cyclase, activation of G protein-coupled inwardly rectifying potassium (GIRK) channels, and inhibition of voltage-gated calcium channels (PubMed: 11595415).