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• W2019436135 abstract "1. The mechanisms of action of antagonists of the gamma-aminobutyric acid C (GABA(C)) receptor picrotoxin, quercetin and pregnanolone were studied. 2. Ionic currents (chloride), mediated through human homomeric GABA rho(1) receptors expressed in Xenopus oocytes, were recorded by two-electrode voltage clamp. 3. Dose-response (D-R) curves and kinetic measurements of GABA rho(1) currents were carried out in the presence or absence of antagonists. Use-dependent actions were also evaluated. 4. Picrotoxin, quercetin and pregnanolone exerted noncompetitive actions. 5. IC(50) values measured at the EC(50) for GABA (1 microM) were as follows: picrotoxin 0.6+/-0.1 microM (Hill coefficient n=1.0+/-0.2); quercetin 4.4+/-0.4 microM (n=1.5+/-0.2); pregnanolone 2.1+/-0.5 microM (n=0.8+/-0.1). 6. These antagonists produced changes only in the slope of the linear current-voltage relationships, which was indicative of voltage-independent effects. 7. The effect of picrotoxin on GABA rho(1) currents was use-dependent, strongly relied on agonist concentration and showed a slow onset and offset. The mechanism was compatible with an allosteric inhibition and receptor activation was a prerequisite for antagonism. 8. The effect of quercetin was use-independent, showed relatively fast onset and offset, and resulted in a slowed time course of the GABA-evoked currents. 9. The effect of pregnanolone was use-independent, presented fast onset and a very slow washout, and did not affect current activation. 10. All the antagonists accelerated the time course of deactivation of the GABA rho(1) currents." @default.
• W2019436135 created "2016-06-24" @default.
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• W2019436135 date "2004-02-01" @default.
• W2019436135 modified "2023-10-14" @default.
• W2019436135 title "Studies on the mechanisms of action of picrotoxin, quercetin and pregnanolone at the GABA<i>ρ</i> ₁ receptor" @default.
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• W2019436135 doi "https://doi.org/10.1038/sj.bjp.0705657" @default.
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