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

FEBS Letters

Abe, Keith Y.¹  Kuo, Paul C.¹ 

[1] Department of Surgery, MSOB X300, Stanford University Medical Center, Stanford, CA 94305, USA

关键词: Nitric oxide;    Cytochrome P-450;    Cimetidine;    Clotrimazole;    Rat hepatocyte;   

DOI  :  10.1016/0014-5793(95)00067-J

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 μM, 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.

【 授权许可】

Unknown