The effects of mucosal application of the short-chain phospholipid didecanoyl-L-alpha-phosphatidylcholine (DDPC; with two saturated 10-carbon acyl chains) on active Na+ transport and transepithelial conductance (G) in the frog skin (Rana temporaria) were investigated. Active Na+ transport was measured as the amiloride-sensitive short-circuit current (ISC) and G was determined from transepithelial voltage-clamp pulses under short-circuit conditions. DDPC dose-dependently inhibited ISC with an ID50 of about 0.05% (w/v) and a maximal effect ( approximately 55%) at >/= 1% DDPC. G increased to steady-state values above control level. Simultaneously, equal increases in unidirectional sucrose permeabilities (PSu; measured from [14C]sucrose fluxes) were observed, and a positive correlation was demonstrated between DDPC-induced changes in PSu and G. Since amiloride did not prevent the increase in G by DDPC, these results suggest that the DDPC-induced increase in G represents an increase in the paracellular shunt conductance. The effects of mucosal DDPC were almost fully reversible within 8 h. The results indicate that DDPC inhibits amiloride-sensitive Na+ channels in the apical membrane of the frog skin epithelium and opens a paracellular tight junction pathway. Both effects may be caused by incorporation of DDPC in the apical cell membrane.