Effects of a short-chain phospholipid on ion transport pathways in rabbit nasal airway epithelium.
We investigated the mechanism of interference of mucosal application of the short-chain phospholipid didecanoyl-L-alpha-phosphatidylcholine (DDPC; 0.1-0.5%) with ion transport pathways in isolated rabbit nasal airway epithelium (RNAE). Transports of Na+ and Cl- were evaluated from tracer ion fluxes, short-circuit current (Isc), and epithelial conductance (Gt) under short-circuit conditions in Ussing chambers. DDPC rapidly and reversibly abolished net Na+ absorption, reduced control Isc (approximately 110 microA/cm2) by approximately 80%, and induced a small Cl secretion. Intracellular Ca2+ concentration ([Ca2+]i) increased dose dependently and transiently (measured by fura 2 in cultured rabbit airway epithelium), but ionomycin failed to mimic the decrease in Isc. The rise in [Ca2+]i may explain a Ba(2+)-sensitive transient activation of a basolateral K+ conductance. Indomethacin-sensitive prostaglandin E2 production in RNAE increased severalfold, but cyclooxygenase and lipoxygenase inhibitors did not prevent DDPC-induced changes in Isc. DDPC initially decreased control Gt (approximately 13 mS/cm2) by approximately 25% due to inhibition of amiloride-sensitive Na+ channels, and then reversibly increased Gt to approximately 45% above control values. Passive Na+ fluxes increased more than Cl fluxes, suggesting that the increase in Gt is due to formation of a paracellular shunt conductance in parallel with unaffected, anion-selective tight junction channels. The results suggest that DDPC inhibits apical membrane Na+ channels and causes structural changes in tight junctions after incorporation in apical cell membranes.
Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark.
M
M
Röpke
M
M
Hansen
S
S
Carstens
P
P
Christensen
G
G
Danielsen
O
O
Frederiksen
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D004553:Electric Conductivity; D004848:Epithelium / Q000378:metabolism; D005260:Female; D008564:Membrane Potentials; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000494:pharmacology*; D011817:Rabbits; D012964:Sodium / Q000502:physiology*; D026941:Sodium Channel Blockers
D010713:Phosphatidylcholines; D026941:Sodium Channel Blockers; C015132:1,2-didecanoylphosphatidylcholine; D012964:Sodium; D015232:Dinoprostone