Dual signal transduction mechanisms modulate ciliary beat frequency
in upper airway epithelium.
Yang, Bin, Rodney J. Schlosser, Thomas V. McCaffrey.
Department of Otorhinolaryngology, Department of Physiology and
Biophysics, Mayo Clinic, Rochester, MN
APStracts 2:0219L, 1995.
This study investigated the effects of methacholine and terbutaline on
the ciliary beat frequency (CBF) of upper airway epithelium. The CBF
of cultured human adenoid explants was measured using
microphotometry. Methacholine (10-6 M) and terbutaline (10-6 M)
increased CBF a maximum of 23.0 +/- 1.8% (P<0.001) and 16.5 +/-
2.3% (P<0.001). Inhibition of endogenous nitric oxide (NO)
production by L-NAME (10-6 M) abolished the effects of methacholine
in L-arginine free medium (P<0.008). This inhibition was
reversed by addition of L-arginine. There was no inhibition of
terbutaline induced ciliostimulation by L-NAME (P >0.5). KT-5823
(10-6 M), a cGMP kinase inhibitor, significantly inhibited the
effects of methacholine (P<0.0001) but not terbutaline
(P>0.15). H-89 (10-6 M), a cAMP kinase inhibitor, significantly
inhibited terbutaline induced ciliostimulation (P< 0.0001), but
not methacholine induced ciliostimulation (P >0.05). Diclofenac
(10-6 M),a cyclooxygenase inhibitor, significantly inhibited the
effects of methacholine (P<0.0007) but had no effect on
terbutaline induced ciliostimulation (P>.05). These findings
suggest that the CBF of upper airway epithelium is modulated through
at least two distinct pathways. The [beta]2-adrenoceptor produces
ciliary stimulation by a pathway involving increased intracellular
cAMP levels, while the muscarinic receptor increases CBF by a
mechanism involving production of prostaglandins, NO, and cGMP.
Received 17 July 1995; accepted in final form 29 November 1995
APS Manuscript Number L229-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 12 December 95