GABAB

GABAB, or gamma-aminobutyric acid type B receptor, is a metabotropic receptor for the inhibitory neurotransmitter GABA in the central nervous system. It mediates slow, prolonged inhibitory signaling that modulates neuronal excitability and synaptic transmission across diverse brain regions.

The functional GABAB receptor is a heterodimer composed of GB1 and GB2 subunits. GB1 binds GABA but requires GB2 for proper trafficking to the cell surface and for effective G-protein signaling. GB1 exists in multiple splice variants (for example GB1a and GB1b), while GB2 is essential for coupling to G proteins. The receptor is G protein-coupled through Gi/o proteins, leading to inhibition of adenylyl cyclase, activation of GIRK channels causing postsynaptic hyperpolarization, and reduced presynaptic voltage-gated calcium channel opening to decrease neurotransmitter release.

Distribution and function of GABAB receptors are widespread in the brain, including the cortex, hippocampus, thalamus, cerebellum, and spinal cord. They are found at both presynaptic and postsynaptic sites and participate in regulating synaptic strength, modulating pain, learning and memory, motor control, and sleep. By dampening excessive neuronal activity, GABAB signaling contributes to the overall balance of cortical networks and can influence plasticity and network oscillations.

Pharmacology and clinical relevance: endogenous GABA activates GABAB receptors, and synthetic agonists such as baclofen are used clinically as muscle relaxants to treat spasticity. Antagonists like CGP55845 have been used in research to study receptor function. GABAB receptors can be modulated by allosteric ligands, and compounds acting at these receptors are explored for pain, anxiety, addiction, and withdrawal syndromes. Common side effects of agonists include sedation, dizziness, and muscle weakness.