Connexin mimetic peptides reversibly inhibit Ca2+signaling through gap junctions in airway cells

Abstract

The effect of peptides with sequences derived from connexins, the constituent proteins of gap junctions, on mechanically stimulated intercellular Ca2+signaling in tracheal airway epithelial cells was studied. Three peptides with sequences corresponding to connexin extracellular loop regions reversibly restricted propagation of Ca2+ waves to neighboring cells. Recovery of communication began within 10 min of removal of the peptides, with inhibition totally reversed by 20–40 min. The peptides were shown to be more effective in inhibiting Ca2+ waves than glycyrrhetinic acid or oleamide. Inhibition of intercellular Ca2+ waves by connexin mimetic peptides did not affect the Ca2+ response to extracellular ATP. Although the intracellular Ca2+ response of tracheal epithelial cells to ATP was greatly reduced by either pretreatment with high doses of ATP or application of apyrase, mechanically stimulated intercellular Ca2+ signaling was not affected by these agents. We conclude that connexin mimetic peptides are effective and reversible inhibitors of gap junctional communication of physiologically significant molecules that underlie Ca2+wave propagation in tracheal epithelial cells and propose a potential mechanism for the mode of action of mimetic peptides.