Gamma-aminobutyric acid receptors and efflux transporters (GABA receptors and ABC transporters)

Gamma-aminobutyric acid (GABA) receptors and efflux transporters represent a functional grouping of proteins critical for inhibitory neurotransmission and the pharmacokinetics of central nervous system (CNS) drugs. GABA receptors, categorized into ionotropic GABA-A and metabotropic GABA-B types, serve as the primary mediators of inhibitory signals in the vertebrate brain, regulating neuronal excitability and muscle tone (StatPearls: Physiology, GABA Receptor; UniProt: P14867). Efflux transporters, particularly members of the ATP-binding cassette (ABC) family like P-glycoprotein (P-gp), are membrane proteins that actively pump xenobiotics out of cells, including the endothelial cells of the blood-brain barrier (UniProt: P08183). In clinical practice, these two systems are often linked in the study of drug-resistant epilepsy, where the overexpression of efflux transporters prevents GABAergic anticonvulsants from reaching their target receptors in the brain (PubMed: 22516059). Therapeutic strategies targeting this complex involve modulating GABAergic tone while simultaneously addressing or bypassing efflux transporter activity to overcome pharmacoresistance (PubMed: 25839135).

Other names

GABAergic system and multidrug resistance proteinsGABA receptors and P-glycoproteinGABA-ABC transporter complex

Positive allosteric modulation of GABA-A receptors; agonism of GABA-B receptors; inhibition of GABA transaminase or reuptake; and inhibition of ATP-binding cassette (ABC) efflux transporters to increase drug CNS penetration.