Leukotrienes mediate 5-hydroxytryptamine-induced plasma extravasation in the rat knee joint via CysLT-type receptors.
OBJECTIVE AND DESIGN: The aim of this study was to investigate whether leukotrienes synthesized by 5-lipoxygenase (5-LO) and acting via leukotriene (LT) receptors contribute to 5-hydroxytryptamine (5-HT)-induced knee joint plasma extravasation (PE). MATERIALS AND METHODS: Knee joints of rats under anesthesia were perfused with 5-HT and synovial vascular Evans Blue dye leakage was measured spectrophotometrically. A series of 5-LO inhibitors and LT receptor antagonists were investigated for their ability to inhibit 5-HT-induced synovial PE. RESULTS: Inhibitors of 5-LO (NDGA and REV 5901) significantly attenuated 5-HT-induced plasma extravasation. MK 571, LY 171883, BAY u9773 (CysLT receptor antagonists) and REV 5901 (a CysLT receptor antagonist and a 5-LO inhibitor) were equally effective in inhibiting 5-HT-induced PE, indicating that leukotrienes mediate 5-HT-induced PE via CysLT receptors. In contrast, antagonists selective for LTB(4) receptors (BLT(1) and BLT(2) receptors) failed to reduce 5-HT-induced PE. CONCLUSIONS: These results demonstrate that leukotrienes, specifically cysteinyl-leukotrienes contribute to synovial plasma extravasation and suggest that leukotrienes act downstream of 5-HT in the inflammatory cascade.[1]References
- Leukotrienes mediate 5-hydroxytryptamine-induced plasma extravasation in the rat knee joint via CysLT-type receptors. Wang, Y., Mitchell, J., Sharma, M., Gabriel, A., Moriyama, K., Palmer, P.P. Inflamm. Res. (2004) [Pubmed]
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