Cyclic AMP (cAMP) represents an important cellular signalling molecule. We analysed the effect of dibutyryl cAMP (db-cAMP), a cell-permeable and stable derivative of cAMP, on the regulation and expression of cyclo-oxygenase 2, inducible NO synthase and argininosuccinate synthetase. We observed different transcriptional regulation of these enzymes depending on the db-cAMP concentration used. Low concentrations of db-cAMP in the range 10-50 μM elevated levels of cyclo-oxygenase 2 mRNA, protein and activity, but not the respective mRNA and protein concentrations of the inducible NO synthase or argininosuccinate synthetase. At higher concentrations a massive induction of the latter two enzymes was also apparent. Expression of prostacyclin synthase and argininosuccinate lyase, secondary enzymes of NO-and prostanoid-forming pathways, was not stimulated by db-cAMP. Prostaglandin E2, known to be an intracellular physiological trigger of cAMP formation, stimulated only cyclo-oxygenase 2 expression and activity at a concentration of 10 μM, and not inducible NO synthase. The induction of the mRNA for the transcription factors JunB and p65, a component of the NFĸB complex, by prostaglandin treatment of the cells might be a possible mechanistic explanation for this observation.
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January 1996
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Research Article|
January 15 1996
Effect of cyclic AMP and prostaglandin E2 on the induction of nitric oxide- and prostanoid-forming pathways in cultured rat mesangial cells
Rolf M. NÜSING;
Rolf M. NÜSING
§
*Medical Centre of Pediatrics, University Hospital Marburg, 35033 Marburg, Germany
§To whom correspondence should be addressed at: Children's Hospital University of Marburg, Deutschhausstraße 12, 35037 Marburg, Germany.
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Thomas KLEIN;
Thomas KLEIN
*Medical Centre of Pediatrics, University Hospital Marburg, 35033 Marburg, Germany
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Josef PFEILSCHIFTER;
Josef PFEILSCHIFTER
†Department of Pharmacology, Biozentrum, University of Basel, Klingelbergstraße 70, 4056 Basel, Switzerland
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Volker ULLRICH
Volker ULLRICH
‡University of Konstanz, Faculty of Biology, P.O. Box 5560, 78434 Konstanz, Germany
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Publisher: Portland Press Ltd
Received:
May 19 1995
Revision Received:
August 31 1995
Accepted:
September 13 1995
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1996
1996
Biochem J (1996) 313 (2): 617–623.
Article history
Received:
May 19 1995
Revision Received:
August 31 1995
Accepted:
September 13 1995
Citation
Rolf M. NÜSING, Thomas KLEIN, Josef PFEILSCHIFTER, Volker ULLRICH; Effect of cyclic AMP and prostaglandin E2 on the induction of nitric oxide- and prostanoid-forming pathways in cultured rat mesangial cells. Biochem J 15 January 1996; 313 (2): 617–623. doi: https://doi.org/10.1042/bj3130617
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