cAMP and Ca²⁺ signaling in secretory epithelia: crosstalk and synergism

Cell Calcium. 2014 Jun;55(6):385-93. doi: 10.1016/j.ceca.2014.01.006. Epub 2014 Feb 7.


The Ca(2+) and cAMP/PKA pathways are the primary signaling systems in secretory epithelia that control virtually all secretory gland functions. Interaction and crosstalk in Ca(2+) and cAMP signaling occur at multiple levels to control and tune the activity of each other. Physiologically, Ca(2+) and cAMP signaling operate at 5-10% of maximal strength, but synergize to generate the maximal response. Although synergistic action of the Ca(2+) and cAMP signaling is the common mode of signaling and has been known for many years, we know very little of the molecular mechanism and mediators of the synergism. In this review, we discuss crosstalk between the Ca(2+) and cAMP signaling and the function of IRBIT (IP3 receptors binding protein release with IP3) as a third messenger that mediates the synergistic action of the Ca(2+) and cAMP signaling.

Keywords: Calcium signaling; Duct epithelia; IRBIT; Synergism.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Calcium Signaling*
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Epithelium / metabolism*
  • Humans
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Membrane Transport Proteins / metabolism


  • Inositol 1,4,5-Trisphosphate Receptors
  • Membrane Transport Proteins
  • Inositol 1,4,5-Trisphosphate
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases