GABAB1

GABAB1, also known as GB1, is a subunit of the GABA-B receptor, a metabotropic G protein-coupled receptor that mediates inhibitory signaling in the central nervous system. The functional GABA-B receptor is an obligate heterodimer composed of GABAB1 and GABAB2 (GB2). GABAB1 binds the neurotransmitter GABA but requires GB2 for proper trafficking to the cell surface and for efficient coupling to G proteins. The receptor signals through Gi/o proteins to inhibit adenylyl cyclase, reduce cAMP formation, activate GIRK potassium channels, and suppress voltage-gated calcium channels, thereby dampening neuronal excitability.

GABAB1 is encoded by the GABBR1 gene and exists as multiple isoforms generated by alternative splicing, notably GABAB1a and GABAB1b. The GABAB1a isoform contains two N-terminal sushi domains that influence subcellular targeting, favoring presynaptic localization, whereas GABAB1b lacks these domains and is enriched postsynaptically. Both isoforms must pair with GABAB2 to form a functional receptor complex.

Distribution and function: GABA-B receptors are widely expressed in the brain and spinal cord, where they modulate synaptic transmission and neural network activity. They participate in processes such as regulation of neurotransmitter release, modulation of synaptic plasticity, and control of muscle tone and pain signaling through pharmacological agents like baclofen.

Clinical and research relevance: The GABA-B system is a target for pharmacological intervention; the agonist baclofen is used clinically to treat spasticity and related conditions. GABA-B signaling has been investigated in relation to epilepsy, anxiety, addiction, and other CNS disorders, and continues to be a focus of research for potential analgesic and cognitive applications.