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• W2023889119 abstract "In voltage clamped cultured hippocampal neurons, application of γ-aminobutyric acid (GABA) or pentobarbitone induced chloride current in a dose-dependent manner. The dose dependence of these agonists were well described by ED50 and Hill coefficients of 14.7 ± 7 μM and 1.2 ± 0.5, and 299 ± 17.3 μM and 1.6 ± 0.1, for GABA and pentobarbitone, respectively. The effects of two GABAA receptor antagonists, bicuculline and 2-(3-carboxypropyl)-3-amino-6-methoxyphenyl-pyridazinium bromide (SR95531) were evaluated by coapplication of increasing concentrations of the antagonists with a fixed equipotent (approximately ED30) dose of GABA or pentobarbitone. Both bicuculline and SR95531 blocked the GABA induced current with ID50 and Hill coefficients of 0.74 ± 0.07 μM and 0.96 ± 0.07, and 0.44 ± 0.02 μM and 1.22 ± 0.06, respectively. Bicuculline similarly blocked the pentobarbitone induced current with a ID50 and Hill coefficient of 0.69 ± 0.04 μM and 1.2 ± 0.1. However, pentobarbitone induced current was poorly blocked by SR95531 retaining 86.5% of current amplitude at a concentration of SR95531, 200 times the IC50 for GABA induced current. Current induced by etomidate, another intravenous general anesthetic with GABAA receptor agonistic property, is likewise resistant to SR95531 blockade. Three-dimensional modeling of bicuculline and SR95531 with alignment of the molecules along the suggested GABA-receptor binding moiety indicates that these two antagonist molecules have distinct steric properties. We suggest that GABA and pentobarbitone act at nearby but non-identical sites on the hippocampal GABAA receptor to open the chloride ionophore, and that these sites can be distinguished by bicuculline and SR95531. This is the first demonstration that the prototypic GABAA site antagonists bicuculline and SR95531 have different effects on currents induced by GABA and pentobarbitone." @default.
• W2023889119 created "2016-06-24" @default.
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• W2023889119 modified "2023-09-25" @default.
• W2023889119 title "The differential antagonism by bicuculline and SR95531 of pentobarbitone-induced currents in cultured hippocampal neurons" @default.
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• W2023889119 doi "https://doi.org/10.1016/0014-2999(96)00156-2" @default.
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