GABAA Receptor Chloride Ion Channels

International Union of Pharmacology. LXX. Subtypes of γ-Aminobutyric AcidAReceptors: Classification on the Basis of Subunit Composition, Pharmacology, and Function. Update

“…Barnard et al (1998) listed approximately 20 chemical classes of ligand that bind to the benzodiazepine (BZ) site on GABA A -R, including the structures of approximately 40 compounds. Additional chemical classes of ligands are listed in Gardner et al (1993), Olsen and Gordey (2000), Sieghart and Ernst (2005), Atack (2005), and Whiting (2006), which should be consulted for chemical names and structures. In each of these chemical classes compounds are available that enhance (positive allosteric modulators or BZ site agonists) or reduce (negative allosteric modulators or inverse BZ site agonists) GABA-induced chloride ion flux via the same BZ binding site.…”

“…Receptors containing the γ 2 subunit exhibit a higher BZ sensitivity than those containing the γ 1 subunit (Sieghart, 1995; Khom et al, 2006); the γ 3-containing GABA A -Rs are modulated by some BZ ligands but with altered selectivity from those incorporating the γ 2 subunit (Sieghart, 1995; Hevers and Lüddens, 1998). The BZ-sensitive GABA A -Rs can be further subdivided, in that receptors containing the α 1 subunit have a higher sensitivity to a subpopulation of BZ site ligands, the benzodiazepines quazepam and cinolazepam (Sieghart, 1989) or nonbenzodiazepines such as zolpidem (an imidazopyridine) and a few others, including CL218-872 (triazolopyridazine), zaleplon, and indiplon, and abecarnil ( β -carboline), (Olsen and Gordey, 2000; Korpi et al, 2002; Sieghart and Ernst, 2005). Furthermore, receptors containing the α 2 or α 3 subunit have an intermediate affinity for zolpidem, whereas those containing α 5 have very low affinity for this drug.…”

Identification of the Bovine γ-Aminobutyric Acid Type A Receptor α Subunit Residues Photolabeled by the Imidazobenzodiazepine [3H]Ro15-4513

“…Interactions of ␥-aminobutyric acid (GABA) with GABA A receptors are modulated by many drugs including benzodiazepines, barbiturates, anesthetics, alcohols, and neurosteroids (8,9). Benzodiazepines are of significant therapeutic interest and are among the most widely prescribed drugs in the world, used to treat anxiety and insomnia, to induce anesthesia, and to reduce seizure activity.…”

Gamma-Aminobutyric Acid (GABA) Inhibits α-Melanocyte-Stimulating Hormone-Induced Melanogenesis through GABAA and GABAB Receptors

“…There are 16 genes responsible for the synthesis of GABA A receptors, including several subunits, such as α1-6, β1-3, γ1-3, δ, ε, θ, and π, while three genes are responsible for the synthesis of rho (ρ) subunits of GABA C (a subclass of the GABA A receptor) [ 18 ]. Allosteric and orthosteric activation of GABA A and GABA c stimulates chloride channels associated with the modulation of anxiety, vigilance, memory, and learning [ 19 , 20 ]. Unlike GABA A and GABA C , GABA B is a metabotropic guanine nucleotide-binding protein couple receptor (GPCR) comprising two subunits, GABA B1 and GABA B2 .…”