Jpn. J. Pharmacol. 72 (2), 191-193 (1996)

Effect of Ebselen on Bovine and Rat Nitric Oxide Synthase Activity Is Modified by Thiols

Ryuichi Hattori (1,#), Yoshiki Yui (1), Eiji Shinoda (1), Reiko Inoue (1), Takeshi Aoyama (1), Hiroyuki Masayasu (2), Chuichi Kawai (3) and Shigetake Sasayama (1)

(1) Third Division, Department of Internal Medicine, Faculty of Medicine, Kyoto University, Kyoto 606-01, Japan (2) Medical Research & Development Department III, Daiichi Pharmaceutical Co., Ltd., Tokyo 134, Japan (3) Kyoto University, Kyoto 606-01, Japan (#) Present address: Division of Emergency Medicine, Kyoto University Hospital, Kyoto 606-01, Japan

Abstract: The inhibition of nitric oxide synthase (NOS) by ebselen, 2-phenyl-1,2-benzisoselenazole- 3(2H)-one, was reversed by the addition of 10-5 M dithiothreitol, suggesting that ebselen reacts with a critical thiol group of NOS in the inhibitory mechanism. In the presence of 10-4 to 10-3 M dithiothreitol, ebselen dose-dependently enhanced NOS activity, implicating another interaction of ebselen with NOS under these conditions. Thus, the effect of ebselen on the NOS activity is modified by thiols.

Keywords: Nitric oxide synthase, Ebselen, Thiol

Copyright© The Japanese Pharmacological Society 1996

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