The neurosteroid allopregnanolone sulfate inhibits Nav1.3 α subunit-containing voltage-gated sodium channels, expressed in Xenopus oocytes

Takafumi Horishita; Nobuyuki Yanagihara; Susumu Ueno; Dan Okura; Reiko Horishita; Tomoko Minami; Yuichi Ogata; Yuka Sudo; Yasuhito Uezono; Takashi Kawasaki

Journal of Pharmacological Sciences (May 2018)

The neurosteroid allopregnanolone sulfate inhibits Nav1.3 α subunit-containing voltage-gated sodium channels, expressed in Xenopus oocytes

Takafumi Horishita,
Nobuyuki Yanagihara,
Susumu Ueno,
Dan Okura,
Reiko Horishita,
Tomoko Minami,
Yuichi Ogata,
Yuka Sudo,
Yasuhito Uezono,
Takashi Kawasaki

Affiliations

Takafumi Horishita: Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, Fukuoka, 807-8555, Japan; Corresponding author. Fax: +81 93 601 2910.
Nobuyuki Yanagihara: School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, Fukuoka, 807-8555, Japan
Susumu Ueno: Department of Occupational Toxicology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, Fukuoka, 807-8555, Japan
Dan Okura: Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, Fukuoka, 807-8555, Japan
Reiko Horishita: Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, Fukuoka, 807-8555, Japan
Tomoko Minami: Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, Fukuoka, 807-8555, Japan
Yuichi Ogata: Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, Fukuoka, 807-8555, Japan
Yuka Sudo: Department of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan
Yasuhito Uezono: Cancer Pathophysiology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuouku, Tokyo, 104-0045, Japan
Takashi Kawasaki: Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu, Fukuoka, 807-8555, Japan

Journal volume & issue: Vol. 137, no. 1
pp. 93 – 97

Abstract

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The neurosteroid allopregnanolone has potent analgesic effects, and its potential use for neuropathic pain is supported by recent reports. However, the analgesic mechanisms are obscure. The voltage-gated sodium channels (Nav) α subunit Nav1.3 is thought to play an essential role in neuropathic pain. Here, we report the effects of allopregnanolone sulfate (APAS) on sodium currents (INa) in Xenopus oocytes expressing Nav1.3 with β1 or β3 subunits. APAS suppressed INa of Nav1.3 with β1 and β3 in a concentration-dependent manner (IC50 values; 75 and 26 μmol/L). These results suggest the possible importance of Nav1.3 inhibition for the analgesic mechanisms of allopregnanolone. Keywords: Allopregnanolone sulfate, Voltage-gated sodium channel α subunit Nav1.3, Neuropathic pain

Published in Journal of Pharmacological Sciences

ISSN: 1347-8613 (Print)
Publisher: Elsevier
Country of publisher: Japan
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/journal-of-pharmacological-sciences

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