Early and late tracheobronchial plasma exudation by platelet-activating factor administered to the airway mucosal surface in guinea pigs: effects of WEB 2086 and enprofylline.
The effects of the platelet-activating factor (PAF) antagonist, WEB 2086, and the xanthine, enprofylline, on PAF-induced plasma exudation in tracheobronchial airways has been studied in guinea pigs. Superfusion of PAF (4 nmol) onto the tracheal mucosal surface caused a significant exudation of the i.v. plasma tracers [131I]albumin and fluorescein isothiocyanate-dextran (fluorescein-labeled dextran MW 156 kDa) during the first 15 min after PAF (early response) and also 5 hr later (late response). The early, but not the late, response could be identified histologically by a particulate tracer (carbon given i.v.) which was trapped in submucosal leaky vessels. WEB 2086 [3 mg (6.6 mumol)/kg] caused significant attenuation of both the early plasma exudative response (with loss of carbon-labeled vessels) and the late plasma exudative response to PAF. The late response was equally well attenuated by enprofylline [4.85 mg (25 mumol)/kg] given before PAF. It is concluded that PAF-induced late (as well as early) plasma exudative responses in guinea pig tracheobronchial airways are the result of specific receptor activation by topical PAF and that the antiasthma xanthine enprofylline can inhibit this PAF-induced late response. Our data suggest that particulate tracers, such as carbon, cannot detect microvessels involved in the ongoing late phase exudative response to PAF.
O'Donnell
S R
SR
Department of Physiology & Pharmacology, University of Queensland, Brisbane, Australia.
Erjefält
I
I
Persson
C G
CG
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects*; D006168:Guinea Pigs; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects*; D014230:Triazoles / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology*
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; D014970:Xanthines; C052518:WEB 2086; C034347:enprofylline