Dual signal transduction mechanisms modulate ciliary beat frequency in upper airway epithelium.
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 nitro-L-arginine methyl ester (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 guanosine 3',5'-cyclic monophosphate (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 > 0.05). 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.
Yang
B
B
Department of Otorhinolaryngology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Schlosser
R J
RJ
McCaffrey
T V
TV
D000234:Adenoids / Q000187:drug effects / Q000502:physiology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D002923:Cilia / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016210:Methacholine Chloride / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D015398:Signal Transduction; D013726:Terbutaline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D016861:Cyclooxygenase Inhibitors; D016210:Methacholine Chloride; D009569:Nitric Oxide; D000242:Cyclic AMP; D006152:Cyclic GMP; D013726:Terbutaline