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(-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.
Hattori
R
R
Third Division, Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Yui
Y
Y
Shinoda
E
E
Inoue
R
R
Aoyama
T
T
Masayasu
H
H
Kawai
C
C
Sasayama
S
S
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001393:Azoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002417:Cattle; D004229:Dithiothreitol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D054833:Isoindoles; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D016566:Organoselenium Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D013439:Sulfhydryl Reagents / Q000494:pharmacology*
D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D013439:Sulfhydryl Reagents; C042986:ebselen; D019001:Nitric Oxide Synthase; D004229:Dithiothreitol