Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Amann, R; Schuligoi, R; Peskar, BA.
Effects of COX-1 and COX-2 inhibitors on eicosanoid biosynthesis and the release of substance P from the guinea-pig isolated perfused lung.
Inflamm Res. 2001; 50(1):50-53
Doi: 10.1007%2Fs000110050724
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- Führende Autor*innen der Med Uni Graz
- Amann Rainer
- Co-Autor*innen der Med Uni Graz
- Peskar Bernhard
- Schuligoi Rufina
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- Abstract:
- OBJECTIVE: In the guinea-pig isolated perfused lung, co-administration of bradykinin (BK) and histamine causes the release of pro-inflammatory neuropeptides, an effect that is largely dependent on BK-induced formation of prostaglandins. Since it is known that at least two isoenzymes, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) catalyse the conversion of arachidonic acid to prostaglandins (PGs) and thromboxanes, the present study aimed at investigating the effect of selective COX-1 and COX-2 inhibitors on the evoked release of substance P (SP). MATERIAL AND METHODS: Lungs were vascularly perfused with oxygenated physiological salt solution containing peptidase inhibitors. BK (0.1 microM) and histamine (100 microM) were added to the perfusate for 10 min and 5 min, respectively. The concentrations of 6-keto-PGF1alpha, cysteinyl-leukotriene (LT), and SP were determined in the outflow by radioimmunoassay. RESULTS: In non-stimulated preparations, indomethacin (2 microM) and the selective COX-1 inhibitor SC-560 (0.03-1 microM) reduced basal release of 6-keto-PGF1alpha, without significantly affecting the release of cysteinyl-LT and SP. The selective COX-2 inhibitors NS-398 (1 microM) or DFU (10 microM) had no significant effect on the basal release of eicosanoids or SP. Co-administration of BK and histamine caused a pronounced increase in the concentration of 6-keto-PGF1alpha and cysteinyl-LT, and SP in the effluate. Under these conditions, indomethacin as well as SC-560 reduced the release of 6-keto-PGF1alpha, enhanced cysteinyl-LT release, and attenuated the release of SP. In contrast, the selective COX-2 inhibitors NS 398 and DFU had no significant effect on the stimulated release of eicosanoids or SP. CONCLUSIONS: These results suggest that in the isolated guinea-pig lung, basal prostanoid biosynthesis as well as BK-induced stimulation of prostanoid formation and subsequent facilitation of histamine-induced SP release is primarily mediated by COX-1 without detectable involvement of COX-2.
- Find related publications in this database (using NLM MeSH Indexing)
- 6-Ketoprostaglandin F1 alpha - metabolism
- Animals - metabolism
- Bradykinin - pharmacology
- Cyclooxygenase 1 - pharmacology
- Cyclooxygenase 2 - pharmacology
- Cyclooxygenase 2 Inhibitors - pharmacology
- Cyclooxygenase Inhibitors - pharmacology
- Cysteine - metabolism
- Eicosanoids - biosynthesis
- Female - biosynthesis
- Guinea Pigs - biosynthesis
- Indomethacin - pharmacology
- Inflammation Mediators - metabolism
- Isoenzymes - antagonists and inhibitors
- Leukotriene C4 - metabolism
- Leukotrienes - metabolism
- Lung - metabolism
- Male - metabolism
- Nitrobenzenes - pharmacology
- Prostaglandin-Endoperoxide Synthases - pharmacology
- Pyrazoles - pharmacology
- Substance P - secretion
- Sulfonamides - pharmacology
- Find related publications in this database (Keywords)
- bradykinin
- prostaglandins
- histamine
- tachykinin
- neurogenic inflammation