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.
Third Division, Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
R
R
Hattori
Y
Y
Yui
E
E
Shinoda
R
R
Inoue
T
T
Aoyama
H
H
Masayasu
C
C
Kawai
S
S
Sasayama
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