DECREASE OF CILIARY BEAT FREQUENCY BY PLATELET-ACTIVATING-FACTOR - PROTECTIVE EFFECT OF KETOTIFEN

The ciliary beat frequency (CBF) of the tracheal epithelial cells cont rols in part the respiratory tract mucociliary transport efficiency, W e investigated the effects on CBF of PAF-acether (PAF) and its metabol ite/precursor lyso-PAF. Guinea-pig tracheal rings were incubated for 3 to 6 h with 1 mu M PAF (C16, C18, C16/C18: 80/20%), lyso-PAF C16 or l yso-phosphatidylcholine (LPC). CBF changes were assessed by microphoto oscillography (mean number of measures per ring = 14). We also examine d 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, CBT of control rings exposed to vehi cle only from 0 to 6 h showed no significant statistical variations (h ertz, mean +/- SEM): 10.8 +/- 0.1 (n of measures = 890). By contrast, 1 mu M C16, C18, and C16/C18 PAF significantly inhibited CBF after 3 t o 6 h 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 res pectively; ANOVA analysis, p < 0.001 from control). Al the same concen tration, lyso-PAF also inhibited CBF, 9.5 +/- 0.1 in = 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 mu M) also suppressed the CBF inhibitor y effect of PAF and lyso-PAF. Incubation of [H-3]PAF with tracheal rin gs from 10 min to 6 h resulted in its partial metabolism (25%) into [H -3]lyso-PAF and a compound with a short retention time (10 min). [H-3] lyso-PAF incubated for 3 h with tracheal rings was partially metaboliz ed (10%) into [H-3]PAF and a compound with a short retention time. The PAF-induced decrease of CBF is congruent with its influence on pulmon ary clearance, possibly via a specific receptor. since WEB 2086 abolis hed the effect of PAF. The inhibition of the PAF-induced CBF decrease by ketotifen may contribute to the therapeutic properties of this anti allergic drug.