TY - JOUR T1 - Correlation of the Apparent Affinities and Efficacies of γ-Aminobutyric Acid<sub>C</sub> Receptor Agonists JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1375 LP - 1380 DO - 10.1124/mol.58.6.1375 VL - 58 IS - 6 AU - Yongchang Chang AU - Douglas F. Covey AU - David S. Weiss Y1 - 2000/12/01 UR - http://molpharm.aspetjournals.org/content/58/6/1375.abstract N2 - γ-Aminobutyric acid (GABA), trans-4-aminocrotonic acid (TACA), muscimol, imidazole-4-acetic acid (I4AA),cis-4-aminocrotonic acid (CACA), and isoguvacine are all GABAC receptor agonists. These compounds have different apparent sensitivities (EC50) and efficacies (I max) on exogenously expressed human ρ1 homomeric GABAC receptors. It is not clear if these differences are due to distinct binding affinities and/or distinct gating kinetics. In this study, using a recently developed single oocyte binding technique, we determined the apparent dissociation constants (K i values) of these compounds from their IC50 values for [3H]GABA displacement. The apparent K i values fell into two distinct groups. The high affinity group was comprised of agonists with longer distances between the nitrogen atom of the amino or imidazole group and the carbon atom of the carboxyl or isoxazole group. The single oocyte binding technique, in conjunction with two-electrode voltage clamp, has allowed a direct correlation of the apparent affinity, efficacy, and potency of agonists on intact functional GABAC receptors. The correlation and coupling of these parameters are discussed in terms of a simple proposed activation mechanism. ER -