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Neurosteroids Allopregnanolone Sulfate and Pregnanolone Sulfate Have Diverse Effect on the α Subunit of the Neuronal Voltage-gated Sodium Channels Na 1.2, Na 1.6, Na 1.7, and Na 1.8 Expressed v v v v in Xenopus Oocytes Takafumi Horishita, M.D., Ph.D., Nobuyuki Yanagihara, Ph.D., Susumu Ueno, M.D., Ph.D., Yuka Sudo, Ph.D., Yasuhito Uezono, M.D., Ph.D., Dan Okura, M.D., Tomoko Minami, M.D., Takashi Kawasaki, M.D., Ph.D., Takeyoshi Sata, M.D., Ph.D. ABSTRACT Background: The neurosteroids allopregnanolone and pregnanolone are potent positive modulators of γ-aminobutyric acid type A receptors. Antinociceptive effects of allopregnanolone have attracted much attention because recent reports have indi- cated the potential of allopregnanolone as a therapeutic agent for refractory pain. However, the analgesic mechanisms of allo- pregnanolone are still unclear. Voltage-gated sodium channels (Na ) are thought to play important roles in inflammatory and neuropathic pain, but there have been few investigations on the effects of allopregnanolone on sodium channels. Methods: Using voltage-clamp techniques, the effects of allopregnanolone sulfate (APAS) and pregnanolone sulfate (PAS) on sodium current were examined in Xenopus oocytes expressing Na 1.2, Na 1.6, Na 1.7, and Na 1.8 α subunits. v v v v Results: APAS suppressed sodium currents of Na 1.2, Na 1.6, and
Anesthesiology – Wolters Kluwer Health
Published: Sep 1, 2014
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