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 (I-sc), and epithelial conductance (G(t)) under short-circuit conditions in Ussing chambers; DDPC rapidly and reversibly abolished net Na+ absorption, reduced central I-sc (similar to 110 mu A/cm(2)) by similar to 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 I-sc. The rise in [Ca2+](i) may explain a Ba2+-sensitive transient activation of a basolateral K+ conductance. Indomethacin-sensitive prostaglandin E(2) production in RNAE increased severalfold, but cyclooxygenase and lipoxygenase inhibitors did not prevent DDPC-induced changes in I-sc. DDPC initially decreased control G(t) (similar to 13 mS/cm(2)) by similar to 25% due to inhibition of amiloride-sensitive Na+ channels, and then reversibly increased G(t) to similar to 45% above control values. Passive Naf fluxes increased more than Cl- fluxes, suggesting that the increase in G(t) 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.