Modulation of airway epithelial cell ciliary beat frequency by nitric oxide.
NOS activity has been recently described in airway epithelial cells. Because these cells are often ciliated we hypothesized that NO modulates airway ciliary beating. CBF was measured in cultured BBECs using video microscopy. L-NMMA, a NOS inhibitor, caused a 40% decrease in CBF following pre-stimulation with isoproterenol (8.5 +/- 0.3 Hz vs 14.6 +/- 0.2 Hz; p < 0.0001) which lasted approximately 60 minutes. Similar attenuation in CBF after isoproterenol pre-treatment was observed with another NOS inhibitor, L-NAME. NOS inhibitor-induced CBF slowing was also observed when cells were pre-stimulated with either bradykinin or substance P and was completely reversed by L-arginine or SNP but not by D-arginine. These observations demonstrate a novel NO-dependent mechanism that upregulates ciliary motility in response to stimulation.
Jain
B
B
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-5300.
Rubinstein
I
I
Robbins
R A
RA
Leise
K L
KL
Sisson
J H
JH
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D001980:Bronchi / Q000502:physiology*; D002417:Cattle; D002923:Cilia / Q000187:drug effects / Q000502:physiology*; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007536:Isomerism; D007545:Isoproterenol / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D019323:omega-N-Methylarginine
D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013373:Substance P; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007545:Isoproterenol; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester