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 ma ximum of 23.0 +/- 1.8% (P < 0.001) and 16.5 +/- 2.3% (P < 0.001). Inhi bition 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 b y addition of L-arginine. There was no inhibition of terbutaline-induc ed ciliostimulation by L-NAME (P > 0.5). KT-5823 (10(-6) M), a guanosi ne 3',5'-cyclic monophosphate (cGMP) kinase inhibitor, significantly i nhibited the effects of methacholine (P < 0.0001), but not terbutaline (P > 0.15). H-89 (10(-6) M), a cAMP kinase inhibitor, significantly i nhibited terbutaline-induced ciliostimulation (P < 0.0001), but not me thacholine-induced ciliostimulation (P > 0.05). Diclofenac (10(-6) M), a cyclooxygenase inhibitor, significantly inhibited the effects of me thacholine (P < 0.0007) but had no effect on terbutaline-induced cilio stimulation (P > 0.05). These findings suggest that the CBF of upper a irway epithelium is modulated through at least two distinct pathways. The beta(2)-adrenoceptor produces ciliary stimulation by a pathway inv olving increased intracellular cAMP levels, while the muscarinic recep tor increases CBF by a mechanism involving production of prostaglandin s, NO, and cGMP.