Mechanism of platelet activating factor-induced vascular leakage in the rat trachea.
Platelet activating factor (PAF) is a phospholipid mediator of inflammation and vascular leakage that may be important in the etiology of asthma. We and others have demonstrated that PAF causes vascular leakage in the rat trachea. In the present study, we attempted to determine how PAF mediates this effect. Vascular leakage was quantitated by measuring the amount of intravascular Evans blue dye extravasated into tracheal tissue. Intravenously administered PAF increased vascular leakage, although Lyso-PAF and Enantio-PAF had no effect. PAF-induced vascular leakage was inhibited in a dose-dependent fashion by the PAF receptor blocker WEB 2086. However, PAF-induced vascular leakage was not inhibited by blockade of cyclooxygenase/lipoxygenase, calmodulin, calcium channels, protein kinase C, histamine receptors, or by destruction of peptidergic sensory nerves. We conclude that PAF causes vascular leakage in the rat trachea by a stereospecific receptor-mediated mechanism that does not depend on arachidonic acid metabolites, calcium, protein kinase C, histamine, or peptidergic sensory nerves.
Kirsch
C M
CM
Division of Respiratory Medicine, Santa Clara Valley Medical Center, San Jose, California 95128.
Brokaw
J J
JJ
Prow
D M
DM
White
G W
GW
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects; D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002199:Capillary Permeability / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000502:physiology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D014132:Trachea / Q000098:blood supply*; D014700:Verapamil / Q000494:pharmacology
D002147:Calmodulin; D016861:Cyclooxygenase Inhibitors; D006635:Histamine H2 Antagonists; D010972:Platelet Activating Factor; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D006632:Histamine; D014700:Verapamil; D011493:Protein Kinase C; D002211:Capsaicin; D002118:Calcium