Carvedilol and adrenergic agonists suppress the lipopolysaccharide-induced NO production in RAW 264.7 macrophages via the adrenergic receptors
| Autor: | M, Pekarova, J, Kralova, L, Kubala, M, Ciz, I, Papezikova, T, Macickova, J, Pecivova, R, Nosal, A, Lojek |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Lipopolysaccharides
Dose-Response Relationship Drug Macrophages Adrenergic beta-Antagonists Carbazoles Nitric Oxide Synthase Type II Nitric Oxide Adrenergic Agonists Gene Expression Regulation Enzymologic Cell Line Receptors Adrenergic Propanolamines Mice Animals Carvedilol Adrenergic alpha-Antagonists Nitrites Signal Transduction |
| Zdroj: | Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 60(1) |
| ISSN: | 1899-1505 |
| Popis: | The interaction of adrenergic agonists and/or antagonists with the adrenergic receptors expressed on immunologically active cells including macrophages plays an important role in regulation of inflammatory responses. Our study investigated the effects of carvedilol, a unique vasodilating beta-adrenergic antagonist, and endogenous adrenergic agonists (adrenalin, noradrenalin, and dopamine) and/or antagonists (prazosin, atenolol) on lipopolysaccharide-stimulated nitric oxide (NO) production from murine macrophage cell line RAW 264.7. The production of NO was determined as the concentration of nitrites in cell supernatants (Griess reaction) and inducible nitric oxide synthase (iNOS) protein expression (Western blot analysis). Scavenging properties against NO were measured electrochemically. Carvedilol in a concentration range of 1, 5, 10 and 25 microM inhibited iNOS protein expression and decreased the nitrite concentration in cell supernatants. Adrenalin, noradrenalin or dopamine also inhibited the iNOS protein expression and the nitrite accumulation. Prazosine and atenolol prevented the effect of both carvedilol and adrenergic agonists on nitrite accumulation and iNOS expression in lipopolysaccharide-stimulated cells. These results, together with the absence of scavenging properties of carvedilol against NO, imply that both carvedilol and adrenergic agonists suppress the lipopolysaccharide-evoked NO production by macrophages through the activation and modulation of signaling pathways connected with adrenergic receptors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|