Ciliostimulatory effects mediated by nitric oxide

Ciliostimulation induced by various transmitters has been suggested to be mediated by the release of nitric oxide (NO). Freshly obtained adenoid tissue explants were pre-treated with the nitric oxide synthase (NOS) inhibitor N(G)-nitro L-arginine (L-NNA), to determine whether the ciliostimulators terbutaline, methacholine, substance P, and endothelin-1 require the release of NO to increase ciliary beat frequency (CBF) in vitro. The L-NNA pre-treatment affected the change in CBF induced by each of the ciliostimulators tested. To determine whether cyclic nucleotides also stimulate CBF by inducing the release of NO, an extra series of experiments were performed with dibutyryl cAMP and dibutyryl cGMP, and L-NNA pre-treatment. In contrast to the experiments with the various ciliostimulators, both dibutyryl cAMP and dibutyryl cGMP exerted ciliostimulatory effects that could not be inhibited by L-NNA. The present findings suggest that NO acts as an intermediate messenger in the ciliated epithelium in response to various transmitters and mediators. On the other hand, pre-treatment with the NOS inhibitor L-NNA did not affect ciliary response to the second messengers cAMP and cGMP, thus suggesting that NO dependent mechanisms do not constitute the sole pathway for the stimulation of ciliary function.