Connexin mimetic peptides reversibly inhibit Ca(2+) signaling through gap junctions in airway cells.
The effect of peptides with sequences derived from connexins, the constituent proteins of gap junctions, on mechanically stimulated intercellular Ca(2+) signaling in tracheal airway epithelial cells was studied. Three peptides with sequences corresponding to connexin extracellular loop regions reversibly restricted propagation of Ca(2+) 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 Ca(2+) waves than glycyrrhetinic acid or oleamide. Inhibition of intercellular Ca(2+) waves by connexin mimetic peptides did not affect the Ca(2+) response to extracellular ATP. Although the intracellular Ca(2+) 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 Ca(2+) 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 Ca(2+) wave propagation in tracheal epithelial cells and propose a potential mechanism for the mode of action of mimetic peptides.
Boitano
S
S
Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071-3166, USA. sboitano@uwyo.edu
Evans
W H
WH
D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002450:Cell Communication / Q000187:drug effects; D017630:Connexins / Q000737:chemistry / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014132:Trachea / Q000502:physiology
D017630:Connexins; D010446:Peptide Fragments; D010455:Peptides; D000255:Adenosine Triphosphate; D002118:Calcium