Gamma-aminobutyric acid type B receptor (GABA_B receptor) (GABA_B receptor)

The Gamma-aminobutyric acid type B receptor (GABA_B receptor) is a metabotropic G protein-coupled receptor that mediates slow inhibitory neurotransmission in the central nervous system [StatPearls]. It functions as an obligate heterodimer, typically composed of GABA_B1 and GABA_B2 subunits [UniProt]. Presynaptic GABA_B receptors, often containing the GABA_B1a isoform, act as autoreceptors or heteroreceptors to modulate the release of various neurotransmitters [PubMed]. Upon activation, these receptors trigger the release of G-beta-gamma subunits, which directly inhibit voltage-gated calcium channels (VGCCs), thereby reducing calcium influx and subsequent vesicle fusion [IUPHAR]. This presynaptic mechanism is crucial for controlling synaptic gain and preventing excitotoxicity [PubMed]. The most well-known drug targeting this receptor is baclofen, an agonist used clinically to manage spasticity in conditions like multiple sclerosis [StatPearls]. Beyond spasticity, presynaptic GABA_B receptors are therapeutic targets for alcohol use disorder, chronic pain, and potentially cognitive disorders [PubMed]. Safety concerns associated with GABA_B modulation include sedation, dizziness, and a risk of seizures upon abrupt withdrawal [StatPearls].

Other names

GABAB receptorG-protein coupled GABA receptorMetabotropic GABA receptorGABBRPresynaptic GABA-B receptor

Agonism of the receptor leads to the activation of Gi/o proteins; the G-beta-gamma subunits directly inhibit presynaptic voltage-gated calcium channels, thereby reducing neurotransmitter release [IUPHAR].