Fig. 3.

Inhibition of endogenously expressed ENaCs in mpkCCD and human airway epithelia (HAE) cells by the 11-mer peptide RFLNLIPLLVF. Representative recordings of the effect of the 11-mer (A) and scrambled peptide (B) on I_sc measured in mpkCCD monolayers. Arrows indicate the addition of peptide (in μM) or amiloride (Amil) at 10 μM. C: inhibition of ENaC in mpkCCD cells by the 11-mer peptide RFLNLIPLLVF. A dose-response curve for the peptide RFLNLIPLLVF was generated in mpkCCD cells. I/I_basal represents the ratio of the amiloride-sensitive component of the I_sc following apical application of peptide, relative to the basal amiloride-sensitive current (I/I_basal). ENaC-mediated I_sc was inhibited with an IC₅₀ of 3.5 μM, 95% confidence interval (CI) 2.7–4.5 μM (n = 22). D: human ortholog of γR158-F168 inhibits endogenous ENaC in HAE cells. Inhibition was estimated as the ratio of the amiloride-sensitive I_sc following apical application of peptide (100 μM) relative to the basal amiloride-sensitive I_sc (I/I_basal). Human and mouse peptides significantly inhibited amiloride-sensitive I_sc compared with scrambled peptide (*P < 0.01 and **P < 0.001; Kruskal-Wallis nonparametric ANOVA followed by Dunn's multiple comparisons posttest). Experiments were performed with 3–11 filters per experimental group.