Platelet‐activating factor relaxes ferret tracheal smooth muscle and reduces transepithelial potential difference in vitro

Abstract

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 (O.1-1OpuM) 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.

Polymorphonuclear leukocyte-generated oxygen metabolites decrease beat frequency of human respiratory cilia

“…Although several mediators released by PMNs can have inhibitory effect on ciliary activity [13,28,40], it is extremely difficult, at the moment, to evaluate the role of these products in a complex biological system such as the one used in this study. Furthermore, mediators of inflammation not only can influence ciliary motion directly, but also can induce the release of ROS, as in the case of PAF [13,38,39].…”

PAF‐induced muscarinic cholinoceptor hyperresponsiveness of ferret tracheal smooth muscle and gland secretion in vitro

“…In the previous paper we described the direct effects of platelet activating factor (PAF) on ferret tracheal smooth muscle, submucosal gland secretion, epithelial albumin transport and potential difference (PD) across the trachea (Webber et al, 1992). Perhaps the most important property of PAF is its ability to induce a potent and long-lasting hyperresponsiveness of airway smooth muscle in vivo (Mazzoni et al, 1985;Cuss et al, 1986;Robertson & Page, 1987).…”

“…The description of the ferret trachea in vitro and of the assays for lysozyme and albumin were described in detail in the previous paper (Webber et al, 1992).…”

“…Methacholine was added to the trachea in a buffer which did not contain PAF. All mucus samples were assayed for lysozyme and albumin (Webber et al, 1992). In the second set of experiments, tracheae were set up in pairs, in separate organ baths.…”

Epithelial factors: modulation of the airway smooth muscle tone

“…Recent studies using radioimmunoassay have demonstrated a reduced release of PGE, and PGI, in epithelium-denuded compared with intact tissues under basal conditions (Hay et al, 1988;Folkerts et rzl, 1989). However, stimulation of the tissues with histamine, methacholine, leukotriene D, or platelet-activating factor (PAF) produces conflicting results (Brunelleschi et al, 1987;Hay et (11, 1988;Folkerts et ul, 1989;Webber et al, 1992) where an increased or decreased production of PGE, is observed. Interestingly, PGE, may have different effects -according to the basal tone (Braunstein et ( I / , 1988).…”