Gamma-aminobutyric acid type B receptor subunit 1 (GABBR1) (GABBR1)

Gamma-aminobutyric acid type B receptor subunit 1 (GABBR1) is a critical component of the metabotropic GABA-B receptor, which functions as an obligatory heterodimer with the GABBR2 subunit [1, 2]. As a member of the Class C G protein-coupled receptor family, GABBR1 is primarily responsible for binding the inhibitory neurotransmitter GABA, while GABBR2 facilitates G-protein coupling and surface expression [11, 13]. Activation of the GABBR1/GABBR2 complex mediates slow and prolonged inhibitory signaling in the central nervous system by inhibiting adenylyl cyclase, opening inwardly rectifying potassium channels, and closing voltage-gated calcium channels [1, 11]. This modulation is essential for maintaining the excitatory-inhibitory balance and fine-tuning synaptic transmission [4, 13]. Dysregulation of GABBR1 is associated with several neurological and psychiatric conditions, including severe spasticity, epilepsy, schizophrenia, and alcohol use disorder [4, 9, 13]. Baclofen is the primary clinical drug targeting this receptor, acting as an agonist to alleviate spasticity, though its use is limited by side effects such as sedation and the risk of severe withdrawal symptoms [5, 6, 10]. Recent research also highlights the role of de novo GABBR1 mutations in neurodevelopmental delays and intellectual disability [13, 18].

Other names

GABA(B)R1GABABR1GB1GPRC3AGamma-aminobutyric acid B receptor subunit 1G-protein coupled receptor family C group 3 member A

Activation of the G protein-coupled GABA-B receptor (as a heterodimer with GABBR2), leading to Gi/o-mediated inhibition of adenylyl cyclase, opening of G protein-coupled inwardly rectifying potassium (GIRK) channels, and inhibition of voltage-gated calcium channels.