Cytokine‐mediated production of nitric oxide in isolated rat hepatocytes is dependent on cytochrome P‐450III activity
- 20 February 1995
- journal article
- Published by Wiley in FEBS Letters
- Vol. 360 (1) , 10-14
- https://doi.org/10.1016/0014-5793(95)00067-j
Abstract
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 ( K i = 21 mM, cimetidine; K i = 13 μ M, 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 cytokinemediated hepatocyte synthesis of NO is dependent upon P-450IIIA activity, which functions in a post-translational capacity.Keywords
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