5-Hydroxytryptamine-induced plasma extravasation in the rat knee joint is mediated by multiple prostaglandins.
OBJECTIVE
This study investigated whether prostaglandins (PGs) are involved in 5-hydroxytryptamine (5-HT)-induced synovial plasma extravasation.


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.
Xie
G
G
Department of Anesthesia, University of California, San Francisco, Box 0464, Room S-455, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Wang
Y
Y
Sharma
M
M
Gabriel
A
A
Mitchell
J
J
Xing
Y
Y
Meuser
T
T
Palmer
P Pierce
PP
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology; D018836:Inflammation Mediators / Q000502:physiology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007719:Knee Joint / Q000187:drug effects*; D008297:Male; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D018836:Inflammation Mediators; D007527:Isoenzymes; D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D012701:Serotonin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone