Catecholamines decrease nitric oxide production by cytokine-stimulated hepatocytes

Joy L. Collins*, Yoram Vodovotz, Toshie Yoneyama, Kazuyuki Hatakeyama, Angela M. Green, Timothy R. Billiar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Background. Catecholamines are significantly elevated in inflammatory responses and play a regulatory role in sepsis. Nitric oxide (NO), also a key inflammatory mediator in sepsis, is produced in large amounts by the inducible nitric oxide synthase (iNOS) in the liver. The purpose of this study was to test the hypothesis that catecholamines play a role in the regulation of NO production by hepatocytes. Methods. Primary hepatocytes were isolated from healthy male Sprague-Dawley rats and either cultured with normal medium or stimulated with cytomix (interleukin-1β, interferon-γ, and tumor necrosis factor-α) in the presence or absence of epinephrine or norepinephrine at varying concentrations. Total RNA was isolated 6 hours after treatment and analyzed by Northern blotting for iNOS mRNA. Protein extracts were obtained at 12 hours and were analyzed by Western immunoblotting for iNOS. Cell culture supernatants were analyzed for NO, determined as the stable end-product NO2-, at 24 hours. Results. Epinephrine and norepinephrine significantly decreased NO2- levels in stimulated hepatocytes but had no effect on iNOS mRNA or protein levels. The decrease in NO2- was reproduced by the adenylate cyclase stimulator, forskolin. The catecholamine-induced decrease in NO2- was completely reversed by the protein kinase A inhibitor Rp-8-Br-cyclic adenosine monophosphate. Conclusions. Catecholamines decrease hepatocyte production of NO in response to cytokine stimulation. This effect seems to be due to post-translational events and appears to be mediated in part by cyclic adenosine monophosphate.

Original languageEnglish
Pages (from-to)256-264
Number of pages9
Issue number2
StatePublished - 2001
Externally publishedYes


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