Leukotrienes mediate 5-hydroxytryptamine-induced plasma extravasation in the rat knee joint via CysLT-type receptors.
OBJECTIVE
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).


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.
Wang
Y
Y
Department of Anesthesia and Perioperative Care, University of California, 513 Parnassus Avenue, San Francisco, California 94143, USA.
Mitchell
J
J
Sharma
M
M
Gabriel
A
A
Moriyama
K
K
Palmer
P Pierce
PP
D000818:Animals; D004396:Coloring Agents; D005070:Evans Blue; D007719:Knee Joint / Q000187:drug effects*; D015289:Leukotrienes / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018077:Receptors, Leukotriene / Q000502:physiology*; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology*; D013053:Spectrophotometry; D013582:Synovial Fluid / Q000187:drug effects* / Q000502:physiology
D004396:Coloring Agents; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; D018102:Receptors, Leukotriene B4; D012701:Serotonin; D005070:Evans Blue; C083169:leukotriene D4 receptor