Connexin mimetic peptides reversibly inhibit Ca(2+) signaling through gap junctions in airway cells

Am J Physiol Lung Cell Mol Physiol. 2000 Oct;279(4):L623-30. doi: 10.1152/ajplung.2000.279.4.L623.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Adenosine Triphosphate / physiology
  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • Calcium Signaling
  • Cell Communication / drug effects
  • Connexins / chemistry
  • Connexins / physiology*
  • Gap Junctions / drug effects
  • Gap Junctions / physiology*
  • Kinetics
  • Molecular Sequence Data
  • Organ Culture Techniques
  • Peptide Fragments / pharmacology
  • Peptides / pharmacology*
  • Rabbits
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / physiology*
  • Trachea / physiology


  • Connexins
  • Peptide Fragments
  • Peptides
  • Adenosine Triphosphate
  • Calcium