Endogenous nitric oxide inhibits leukotriene B4 release from rat alveolar macrophages
| Autor: | Ignaz Wessler, Claudia Hey, Gernot Brunn, Kurt Racké |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Leukotriene B4
Lipoxygenase Arachidonic Acids Biology Nitric Oxide Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Phospholipase A2 Macrophages Alveolar medicine Animals Enzyme Inhibitors Calcimycin Cells Cultured Chromatography High Pressure Liquid Pharmacology omega-N-Methylarginine Prostanoid Molecular biology Rats medicine.anatomical_structure chemistry Biochemistry Prostaglandin-Endoperoxide Synthases Alveolar macrophage biology.protein Female Arachidonic acid Nitric Oxide Synthase Pulmonary alveolus |
| Zdroj: | European Journal of Pharmacology. 326:53-60 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/s0014-2999(97)00136-2 |
| Popis: | Effects of endogenous nitric oxide (NO) on the release of mediators of the lipoxygenase and cyclo-oxygenase pathway from rat alveolar macrophages were studied. Alveolar macrophages, freshly isolated or after 18-h culture, were incubated in (amino acid-free) Krebs medium and labelled with [3H]arachidonic acid. The release of [3H]leukotriene B4 and [3H]prostanoids (separated by high performance liquid chromatography) was determined. A 23187 was used as stimulus, as rising intracellular Ca2+ activates directly the phospholipase A2 and lipoxygenase pathway. A 23187 (10 microM) enhanced [3H]leukotriene B4 release from freshly prepared alveolar macrophages about 65-fold, but only 5- to 6-fold from cultured alveolar macrophages. Evoked [3H]leukotriene B4 release and spontaneous [3H]prostanoid release were inhibited when L-arginine (300 microM) was added to the Krebs incubation medium of alveolar macrophages, in which marked NO synthase had been induced by culture with lipopolysaccharides (10 microg/ml). Inhibitory effects of L-arginine were prevented by N(G)-monomethyl-L-arginine (L-NMMA, 100 microM). Inhibition of NO synthase during the culture period by L-NMMA (culture medium, in contrast to Krebs medium, already contains the substrate of NO synthase, L-arginine), resulted in attenuation of the 'culture-dependent' decline of the evoked release of [3H]leukotriene B4 and allowed lipopolysaccharides to cause an increase in spontaneous [3H]prostanoid release (i.e., to induce cyclo-oxygenase activity). In conclusion, in rat alveolar macrophages, endogenous NO appears to inhibit the release of mediators of the cyclo-oxygenase and lipoxygenase pathway through multiple sites of action. |
| Databáze: | OpenAIRE |
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