Gamma-aminobutyric acid B receptor (GABA_B receptor)

The gamma-aminobutyric acid B receptor (GABA_B receptor) is a metabotropic, G protein-coupled receptor (GPCR) for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the central nervous system. Unlike ionotropic GABA receptors (such as GABA_A and GABA_C), which mediate fast synaptic inhibition, GABA_B receptors are responsible for slow and prolonged inhibitory signaling. The functional GABA_B receptor is an obligate heterodimer composed of two subunits: GABA_B1 and GABA_B2. Activation by GABA or agonists like baclofen couples the receptor to Gi/o-type heterotrimeric G proteins, leading to activation of GIRKs, inhibition of calcium channels, and inhibition of adenylyl cyclase. These effects result in decreased neuronal excitability and reduced neurotransmitter release. It plays roles in various physiological processes including regulation of synaptic transmission, behavioral responses to ethanol and GHB, pain perception, gastrointestinal function, and developmental processes in the nervous system. It is highly expressed throughout the central nervous system and in peripheral tissues like the gastrointestinal tract. The GABA_B receptor is implicated in neurological disorders including epilepsy, spasticity, addiction/alcoholism, anxiety disorders, depression, and schizophrenia, making it an attractive drug target.

Gi/o protein-mediated activation of GIRK channels, inhibition of voltage-gated calcium channels, and inhibition of adenylyl cyclase