The ciliary beat frequency (CBF) of the tracheal epithelial cells controls in part the respiratory tract mucociliary transport efficiency. We investigated the effects on CBF of PAF-acether (PAF) and its metabolite/precursor lyso-PAF. Guinea-pig tracheal rings were incubated for 3 to 6 h with 1 μM PAF (C16, C18, C16/C18: 80/20%), lyso-PAF C16 or lyso-phosphatidylcholine (LPC). CBF changes were assessed by microphotooscillography (mean number of measures per ring=14). We also examined the effect on PAF-induced CBF changes of the PAF receptor-antagonist WEB 2086, the anti-asthmatic/anti-anaphylactic drug ketotifen and the anti-histamine H1 pyribenzamine. CBF of control rings exposed to vehicle only from 0 to 6 h showed no significant statistical variations (hertz, mean±SEM): 10.8±0.1 (n of measures=890). By contrast, 1 μM C16, C18, and C16/C18 PAF significantly inhibited CBF after 3 to 6h incubation. C16 and C16/C18 PAF were more potent than C18 PAF (8.8±0.2, n=112, 8.7±0.2, n=64, and 9.6±0.1, n=537 respectively; ANOVA analysis, p<0.001 from control). At the same concentration, lyso-PAF also inhibited CBF, 9.5±0.1 (n=197, p<0.001) but not LPC, 10.5±0.2 (n=127). WEB 2086 inhibited lyso-PAF and C16/18 PAF-induced CBF decrease. Preincubation (20 min) with ketotifen but not with pyribenzamine (1 μM) also suppressed the CBF inhibitory effect of PAF and lyso-PAF. Incubation of [3H]PAF with tracheal rings from 10 min to 6 h resulted in its partial metabolism (25%) into [3H]lyso-PAF and a compound with a short retention time (10 min). [3H]lyso-PAF incubated for 3 h with tracheal rings was partially metabolized (10%) into [3H]PAF and a compound with a short retention time. The PAF-induced decrease of CBF is congruent with its influence on pulmonary clearance, possibly via a specific receptor, since WEB 2086 abolished the effect of PAF. The inhibition of the PAF-induced CBF decrease by ketotifen may contribute to the therapeutic properties of this antiallergic drug.
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