[Intravenous anesthetics, acting on the gamma-amino butric acid (GABA)A receptor, potentiate the herbal medicine "saiko-keishi-to"-induced chloride current].
We have reported that the Japanese herbal medicine "Saiko-Keishi-To" (SK) which is often used for treating epileptic patients activates the GABAA receptor-mediated chloride current (Icl). In the present study, we examined whether the SK-induced Icl could be potentiated by several intravenous anesthetics known to interact with the GABAA receptor, and also examined whether SK could potentiate the GABA-induced Icl. Whole-cell patch-clamp recordings were made from cultured rat dorsal root ganglion cells. The peak amplitude of the Icl evoked by SK (2 mg.ml-1) increased after pentobarbital (50 microM) to 184 +/- 26% (n = 5), diazepam (1 microM) to 166 +/- 29% (n = 5), and propofol (5 microM) to 294 +/- 93% (n = 5) from their respective controls, while the anesthetics did not activate the Icl by themselves. The peak amplitude of the Icl evoked by GABA (10 microM) increased after propofol (5 microM) to 617 +/- 189% of the control (n = 4), but decreased to 84 +/- 7% of the control by SK (0.2 mg.ml-1, n = 4). These results indicate that the SK-induced Icl can be potentiated by the intravenous anesthetics, positive allosteric modulators of the GABAA receptor-Cl- channel complex and that SK is not a positive allosteric modulator, but a partial agonist for the GABAA receptor. Our study thus suggests that the combined use of SK and anticonvulsants such as barbiturates and benzodiazepines may be more effective in treating epileptic patients than SK alone.
Sugiyama
K
K
Department of Anesthesiology, Kurume University School of Medicine.
Kano
T
T
Muteki
T
T
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002478:Cells, Cultured; D002713:Chlorine / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D010424:Pentobarbital / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013268:Stimulation, Chemical
D018686:Anesthetics, Intravenous; D000927:Anticonvulsants; D004365:Drugs, Chinese Herbal; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D002713:Chlorine; C018142:saiko-keishi-to; D010424:Pentobarbital; D003975:Diazepam; D015742:Propofol