We studied the direct effects of nicotine on the ciliary beat frequency (CBF) undisturbed by interference from mucus secretion by using epithelial strips fi'om ferret tracheae which contain no goblet cells and, because the glands were left behind in the submucosa, no gland tissue either. Strips were studied in a chamber perfused with medium M-199 at 37°C at a perfusion rate of 1.6 ml min-1 using a perfusion pump (Braun, Melsungen). CBF was determined photometrically, the signal being subjected to a fast Fourier transformation. We measured CBF continuously for 10 min (5 min with and 5 min without perfusion). Under baseline conditions without nicotine, it decreased from 23.4_+0.8 to 22.2_+0.5 Hz during perfusion and increased fi'om 22.0 _+ 0.8 to 23.3 + 0.8 Hz during the subsequent period without perfusion. Nicotine increased CBF transiently, i.e., the effect was demonstrable only during perfusion, being strongest during the first 3 min of perfusion. At 10-5 M, the increase in CBF was significant only during the 3rd minute, but at •0 .4 and 10 .3 M, CBF was elevated significantly throughout most of the perfusion period compared with control tissues perfused with medium M-199 only. Thus, at 2 min, CBF was 22.8_+0.6 (2+_SE) in tissues perfused with medium M-199 only but was 24.3+0.8 Hz (NS, Student's unpaired t-test), 26.6_+ 0.5 Hz (P= 0.00•), and 26.8 + 1.2 Hz (P = 0.01) in tissues perfused with 10 -5, 10 -4, and 10 .3 M nicotine (dissolved in medium M-199), respectively. We conclude that nicotine stimulates CBF and that the effect is not mediated by a nicotine-induced increase in mucus secretion.Abbreviation. CBF =ciliary beat frequency Cigarette smoke bubbled through the suspending medium has been shown to decrease the ciliary beat frequency (CBF) dramatically in biopsies from human bronchi in vitro [•4], but the shortterm application of cigarette smoke as well as the close intraarterial injection of nicotine caused a transient increase in CBF in vivo [9, •3]. The discrepancy could be explained by differences between the effects of nicotine and of other components of cigarette smoke, by differences in the concentration of nicotine reaching the mucosa, and also by differences between the direct and indirect effects of nicotine. Thus, we have shown previously that nicotine increases mucus secretion [2,3,7,8,11]. Therefore, the effects of nicotine on the CBF may be indirect. CBF may vary because of altered mucus viscosity following increased gland activity. The present study was performed with the aim of identifying the effects of "realistic" concentrations of nicotine on CBF. Direct rather than secondary effects were studied by applying nicotine to a preparation containing only cilia (no mucussecreting elements). We were able to show that nicotine caused a transient increase in CBF which could not be attributed to altered gland secretion.
MethodsIn order to study the direct effects of nicotine, undisturbed by interference from mucus secretion, we used epithelial strips from ferret tracheae. Goblet cells are extremel...