Microvascular leakage induced by substance P in rat urinary bladder: involvement of cyclo-oxygenase metabolites of arachidonic acid.
1. Intravenous administration of substance P (SP) or of the NK1 selective agonist [beta-Ala4, Sar9, Met (O2)11] SP-(4-11) increased vascular permeability in the urinary bladder of urethane-anaesthetized rats, providing evidence for an NK1 receptor-mediated inflammatory response. 2. BW 755C, a dual inhibitor of arachidonate cyclo-oxygenase and lipoxygenase, significantly reduced the plasma extravasation induced by SP, but did not modify the effect of [beta-Ala4, Sar9, Met (O2)11] SP-(4-11). 3. SP-induced microvascular leakage was also inhibited by systemic pretreatment with indomethacin or with the prostaglandin receptor antagonist SC-19220, while it was unaffected by the selective 5-lipoxygenase inhibitor BW A4C or the leukotriene antagonist FPL 55712. 4. Pretreatment of rats with the mast cell degranulating agent compound 48/80 significantly attenuated the inflammatory effect of SP. Indomethacin administration to 48/80-pretreated animals failed to produce further inhibition. 5. These findings indicate that intravascular SP promotes plasma exudation in rat urinary bladder through an NK1-mediated effect on venular permeability and the release of cyclo-oxygenase metabolites of arachidonic acid. The latter effect largely derives from the interaction of the neuropeptide with mast cells.
Abelli
L
L
Faculty of Sciences, Università della Tuscia, Viterbo, Italy.
Nappi
F
F
Perretti
F
F
Maggi
C A
CA
Manzini
S
S
Giachetti
A
A
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology*; D001743:Urinary Bladder / Q000098:blood supply* / Q000187:drug effects; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D002867:Chromones; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors; D010446:Peptide Fragments; C061059:substance P (4-11), beta-Ala(4)-Sar(9)-Met(02)(11)-; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; D016718:Arachidonic Acid; D013373:Substance P; D003189:p-Methoxy-N-methylphenethylamine; C006312:FPL 55712; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin