Role of CNP in human airways: cGMP-mediated stimulation of ciliary beat frequency.
Ciliated airway epithelial cells contribute to mucociliary transport systems via ciliary beating and electrolyte transport mechanisms. Both of these activities are regulated by agonists acting through intracellular calcium- and adenosine 3',5'-cyclic monophosphate (cAMP)-dependent processes (5, 15, 18, 27). This study examines the role of guanosine 3',5'-cyclic monophosphate (cGMP) in the regulation of both ciliary beat frequency (CBF) and electrolyte transport in human airway epithelia (HAE). In a previous report, cGMP production in HAE was observed after 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-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP), but not by sodium nitroprusside. CNP-induced increases in CBF do not appear to be mediated by changes in either intracellular calcium or cAMP levels. Using modified Ussing chambers, we also investigated CNP's potential modulation of sodium and chloride transport rates. Neither CNP, nor SNP, nor 8-BrcGMP altered active ion transport rates. We conclude that CNP regulates ciliary beat via cGMP-dependent mechanisms, whereas no effect of CNP or cGMP on ion transport was detected.
Geary
C A
CA
Department of Medicine, University of North Carolina at Chapel Hill 27599, USA.
Davis
C W
CW
Paradiso
A M
AM
Boucher
R C
RC
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009068:Movement / Q000187:drug effects; D009297:Nasal Mucosa / Q000502:physiology*; D020098:Natriuretic Peptide, C-Type; D009599:Nitroprusside / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology*; D013997:Time Factors
D011506:Proteins; D020098:Natriuretic Peptide, C-Type; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009320:Atrial Natriuretic Factor; D000255:Adenosine Triphosphate; D006152:Cyclic GMP; D007545:Isoproterenol