PAF-induced secretory hyperresponsiveness in the ferret trachea to bradykinin and its pharmacological inhibition.
Both PAF (10 microM) and bradykinin (0.1-10 microM) increased lysozyme (from submucosal gland serous cells (+138 and +45% for PAF, 10 microM, and bradykinin, 1 microM, respectively) and albumin (mainly active epithelial transport; +387 and +108%) outputs into the ferret tracheal lumen in vitro and reduced the negativity of the potential difference (PD: -33 and -17%) across the trachea. Since PAF can cause bronchial smooth muscle hyperresponsiveness, we tested whether these effects were interactive, and if PAF would increase the actions of bradykinin. The bradykinin-induced lysozyme and albumin outputs were more than trebled and the PD change was enhanced by PAF, after the immediate secretory effects of the latter had returned to baseline. The secretory and PD responses to PAF were all prevented by the PAF-antagonist WEB 2086 and by a combination of the free-radical scavengers catalase and SOD, indicating that PAF may act on specific receptors to release free-radicals. Nedocromil sodium inhibited the increase in lysozyme and albumin outputs produced by PAF, but had no effect on the PD response. None of the tracheal responses to bradykinin was modified by WEB 2086, catalase and SOD, or nedocromil sodium. The secretory and PD hyperresponsiveness to bradykinin caused by PAF was prevented by WEB 2086 and by catalase and SOD. Nedocromil sodium greatly inhibited the lysozyme and albumin hyperresponsiveness but had no effect on the PD response. Thus PAF may release more than one type of radical which have differential effects on serous cells and albumin transport compared with PD; nedocromil sodium may act only against the radical causing the secretory effects.
Webber
S E
SE
Department of Physiology, St George's Hospital Medical School, Cranmer Terrace, London, SW17 0RE, U.K.
Kitt
A
A
Yurdakos
E
E
Widdicombe
J G
JG
D000418:Albumins / Q000378:metabolism; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005289:Ferrets; D008297:Male; D009113:Muramidase / Q000378:metabolism; D017835:Nedocromil / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology*
D000418:Albumins; D018927:Anti-Asthmatic Agents; D001381:Azepines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; D017835:Nedocromil; C052518:WEB 2086; D009113:Muramidase; D001920:Bradykinin