ROLE OF CNP IN HUMAN AIRWAYS - CGMP-MEDIATED STIMULATION OF CILIARY BEAT FREQUENCY

Ciliated airway epithelial cells contribute to mucociliary transport s ystems via ciliary beating and electrolyte transport mechanisms. Both of these activities are regulated by agonists acting through intracell ular calcium- and adenosine 3',5'-cyclic monophosphate (cAMP)-dependen t processes (5, 15, 18, 27). This study examines the role of guanosine 3',5'-cyclic monophosphate (cGMP) in the regulation of both ciliary b eat frequency (CBF) and electrolyte transport in human airway epitheli a (HAE). In a previous report, cGMP production in HAE was observed aft er stimulation with either C-type natriuretic peptide (CNP) or sodium nitroprusside (SNP) (6). In this study, CNP was found to increase CBF by 30 +/- 6.9%, and this effect was mimicked by the cGMP analogue, 8-b romoguanosine 3',5'-cyclic monophosphate (8-BrcGMP), but not by sodium nitroprusside. CNP-induced increases in CBF do not appear to be media ted by changes in either intracellular calcium or cAMP levels. Using m odified Ussing chambers, we also investigated CNP's potential modulati on of sodium and chloride transport rates. Neither CNP, nor SNP, nor 8 -BrcGMP altered active ion transport rates. We conclude that CNP regul ates ciliary beat via cGMP-dependent mechanisms, whereas no effect of CNP or cGMP on ion transport was detected.