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

The inhibition of nitric oxide synthase (NOS) by ebselen, 2-phenyl-1, 2-benzisoselenazole-3(2H)-one, was reversed by the addition of 10 M dithiothreitol, suggesting that ebselen reacts with a critical thiol group of NOS in the inhibitory mechanism. In the presence of 10minus;4 to 10minus;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.