The effect of nitric oxide on the permeability of nasal epithelial cells from healthy and asthmatic donors.
BACKGROUND
To see if the higher levels of nitric oxide expired by asthmatics compared to healthy subjects might be of significance to airway function, the effect of nitric oxide and its second messenger, guanosine 3', 5'- cyclic monophosphate (cGMP), on the permeability of human nasal epithelial cells was studied.


METHODS
Cells from healthy and asthmatic donors, collected by swab biopsy, were plated on agar gel before being impaled with a microelectrode to measure their intracellular potential and membrane resistance.


RESULTS
Exposure of cells to 300 mM sodium nitroprusside, a nitric oxide donor, caused a profound fall in both parameters in cells from non-asthmatics but no change in cells from asthmatic subjects. A similar response was seen when cells were exposed to 0.9 mM of the permeable form of cGMP, 8-Br-cGMP. Selective inhibition of ion transport pathways in healthy cells indicated that nitric oxide produced changes in permeability consistent with secretion of anions by the cells.


CONCLUSIONS
Since anion secretion is associated with fluid secretion in the intact epithelium, we suggest that nitric oxide mediates a protective mechanism to remove foreign material from the airway surface. The defective response to nitric oxide seen in asthmatic cells may contribute to the disease by compromising the removal of allergens from the airway.
Baker
Graham
G
School of Biological Sciences, Royal Holloway, University of London, Egham Hill, Egham Surrey TW20 0EX, UK. g.baker@rhbnc.ac.uk
Chetwin
Karen
K
Hayward
Kathryn
K
Bakirtzi
Kyriaki
K
Willman
Melissa
M
D000328:Adult; D000584:Amiloride / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000378:metabolism*; D017609:Barium Compounds / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D004232:Diuretics / Q000378:metabolism; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008564:Membrane Potentials; D008875:Middle Aged; D009297:Nasal Mucosa / Q000166:cytology*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism; D009599:Nitroprusside / Q000378:metabolism; D010539:Permeability; D062367:ortho-Aminobenzoates / Q000378:metabolism
D017609:Barium Compounds; D002121:Calcium Channel Blockers; D002712:Chlorides; D004232:Diuretics; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D062367:ortho-Aminobenzoates; C024986:barium chloride; D009599:Nitroprusside; D009569:Nitric Oxide; D000584:Amiloride; C001209:fenamic acid