Carvedilol and adrenergic agonists suppress the lipopolysaccharide-induced NO production in RAW 264.7 macrophages via the adrenergic receptors.
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.
Institute of Biophysics of the AS CR, Kralovopolska, Kralovopolska 135, Brno, Czech Republic.
M
M
Pekarova
J
J
Kralova
L
L
Kubala
M
M
Ciz
I
I
Papezikova
T
T
Macickova
J
J
Pecivova
R
R
Nosal
A
A
Lojek
D000322:Adrenergic Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology*; D000077261:Carvedilol; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000322:Adrenergic Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D008070:Lipopolysaccharides; D009573:Nitrites; D011412:Propanolamines; D011941:Receptors, Adrenergic; D000077261:Carvedilol; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II