Cytokine-mediated production of nitric oxide in isolated rat hepatocytes is dependent on cytochrome P-450III activity.

Journal Article (Journal Article)

To investigate the role of the cytochrome P-450 system in NO synthesis, cytochrome P-450IIIA, IIE and IA activities were specifically inhibited by cimetidine (IIIA), clotrimazole (IIIA), benzoflavone (IA) and disulfiram (IIE) in a model of cultured rat hepatocytes. Cytokine-induced NO synthesis was significantly decreased in the presence of cimetidine and clotrimazole. Kinetic analysis revealed a non-competitive mode of inhibition (Ki = 21 mM, cimetidine; Ki = 13 microM, clotrimazole). Reverse transcriptase-PCR and immunoblot analysis revealed no significant change in steady state levels of iNOS mRNA and protein expression with P-450IIIA inhibition. Purified iNOS enzyme activity was not altered. These data suggest that cytokine-mediated hepatocyte synthesis of NO is dependent upon P-450IIIA activity, which functions in a post-translational capacity.

Full Text

Duke Authors

Cited Authors

  • Kuo, PC; Abe, KY

Published Date

  • February 20, 1995

Published In

Volume / Issue

  • 360 / 1

Start / End Page

  • 10 - 14

PubMed ID

  • 7533105

International Standard Serial Number (ISSN)

  • 0014-5793

Digital Object Identifier (DOI)

  • 10.1016/0014-5793(95)00067-j


  • eng

Conference Location

  • England