Platelet-activating factor relaxes ferret tracheal smooth muscle and reduces transepithelial potential difference in vitro.
1. The effects of platelet activating factor (PAF) were examined on the smooth muscle tone, mucus volume, lysozyme and albumin outputs and potential difference (PD) across the ferret tracheal wall. 2. PAF (0.1-10 microM) had no direct effect on mucus volume, lysozyme or albumin output from the ferret trachea. PAF produced concentration-dependent relaxations of the tracheal smooth muscle and reductions in PD across the tracheal wall. There was no change in the histological appearance of the trachea after exposure to PAF. 3. The PAF-induced smooth muscle relaxation was not affected by FPL55712, a combination of mepyramine and cimetidine, or by a combination of the oxygen free-radical scavengers catalase and superoxide dismutase (SOD); but was abolished by indomethacin or the PAF-receptor antagonist WEB2086. 4. The PAF-induced reduction in PD was not affected by indomethacin, FPL55712 or mepyramine and cimetidine, but was prevented by catalase and SOD, and by WEB2086. 5. We conclude that PAF relaxes ferret tracheal smooth muscle in vitro by receptor-mediated release of a bronchodilator prostaglandin, possibly PGE2. PAF also reduces PD across the trachea suggesting changes in epithelial function; however, there is no histological epithelial damage after PAF. The reduction in PD with PAF is probably produced by receptor-mediated release of oxygen free-radicals. The cellular source of these free-radicals and of the dilator prostaglandin is unclear.
Webber
S E
SE
Department of Physiology, St George's Hospital Medical School, London.
Morikawa
T
T
Widdicombe
J G
JG
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D004566:Electrodes; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D005289:Ferrets; D066298:In Vitro Techniques; D008297:Male; D009113:Muramidase / Q000032:analysis; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics; D014132:Trachea / Q000187:drug effects
D010972:Platelet Activating Factor; D012710:Serum Albumin, Bovine; D009113:Muramidase