ABSTRACT
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.
Subject(s)
Knee Joint/drug effects , Leukotrienes/physiology , Membrane Proteins/physiology , Receptors, Leukotriene/physiology , Serotonin/pharmacology , Synovial Fluid/drug effects , Animals , Coloring Agents , Evans Blue , Lipoxygenase Inhibitors/pharmacology , Male , Rats , Rats, Sprague-Dawley , Receptors, Leukotriene B4/antagonists & inhibitors , Spectrophotometry , Synovial Fluid/physiologyABSTRACT
OBJECTIVE AND DESIGN: This study investigated whether prostaglandins (PGs) are involved in 5-hydroxytryptamine (5-HT)-induced synovial plasma extravasation. MATERIALS AND METHODS: Male Sprague-Dawley rat knee joints were perfused with 5-HT and synovial capillary Evans Blue dye leakage was measured using spectrophotometry. Cyclooxygenase (COX) inhibitors and PG receptor subtype-selective antagonists were tested for the ability to reduce 5-HT-induced synovial plasma extravasation. RESULTS: 5-HT-induced plasma extravasation was inhibited by indomethacin. The COX-1 selective inhibitor SC-560 and the COX-2 selective inhibitor NS-398 were equally effective, indicating that both isoforms are involved. Antagonists selective for EP1, EP2 and DP receptor subtypes significantly attenuated the 5-HT-induced plasma extravasation. However, antagonists selective for FP, IP and TP subtypes failed to reduce 5-HT-induced plasma extravasation. CONCLUSIONS: These results demonstrate that multiple, but selective, subtypes of PGs mediate synovial plasma extravasation produced by 5-HT, and suggest that PGs act downstream of 5-HT in the inflammatory cascade.