Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. There are two major classes of GABA receptors: the GABA-A and the GABA-B subtype of receptors. GABA-A-Rs are important therapeutic targets for a range of sedative, anxiolytic, and hypnotic agents and are implicated in several diseases including epilepsy, anxiety, depression, and substance abuse. The GABA-A-R is a multimeric subunit complex. To date six alphas, four betas and four gammas, plus alternative splicing variants of some of these subunits, have been identified (Olsen and Tobin, 1990, Whiting et al., 1999, Ogris et al., 2004). Injection in oocytes or mammalian cell lines of cRNA coding for alpha- and beta-subunits results in the expression of functional GABA-A-Rs sensitive to GABA. However, coexpression of a gamma-subunit is required for benzodiazepine modulation. Phosphorylation of serine 408 and serine 409 within the beta3 subunit have been shown to be critical for the functional modulation of beta3 containing recombinant receptors (Brandon et al., 2000).
Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. There are two major classes of GABA receptors: the GABA-A and the GABA-B subtype of receptors. GABA-A-Rs are important therapeutic targets for a range
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