CAMP and Ca²⁺ signaling in secretory epithelia: Crosstalk and synergism

The Ca²⁺ and cAMP/PKA pathways are the primary signaling systems in secretory epithelia that control virtually all secretory gland functions. Interaction and crosstalk in Ca²⁺ and cAMP signaling occur at multiple levels to control and tune the activity of each other. Physiologically, Ca²⁺ and cAMP signaling operate at 5-10% of maximal strength, but synergize to generate the maximal response. Although synergistic action of the Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ and cAMP signaling.