Drug Metabolism and Pharmacokinetics
Online ISSN : 1880-0920
Print ISSN : 1347-4367
ISSN-L : 1347-4367
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Cytochrome P450 is Responsible for Nitric Oxide Generation from NO-Aspirin and Other Organic Nitrates
Yukiko MINAMIYAMAShigekazu TAKEMURASusumu IMAOKAYoshihiko FUNAEShigeru OKADA
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2007 Volume 22 Issue 1 Pages 15-19

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Abstract

  Nitric oxide (NO) biotransformation from NO-aspirin (NCX-4016) is not clearly understood. We have previously reported that cytochrome P450 (P450) plays important role in NO generation from other organic nitrates such as nitroglycerin (NTG) and isosorbide dinitrate (ISDN). The present study was designed to elucidate the role of human cytochrome P450 isoforms in NO formation from NCX-4016, using lymphoblast microsomes transfected with cDNA of human P450 or yeast-expressed, purified P450 isoforms. CYP1A2 and CYP2J2, among other isoforms, were strongly related to NO production from NCX-4016. In fact, these isoforms were detected in human coronary endothelial cells. These results suggest that NADPH-cytochrome P450 reductase and the P450 system participate in NO formation from NCX-4016, as well as other organic nitrates.

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© 2007 by The Japanese Society for the Study of Xenobiotics
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