Regulation of IP$_{3}$ receptors by cyclic AMP

Ca$^{2+}$ and cAMP are ubiquitous intracellular messengers and interactions between them are commonplace. Here the effects of cAMP on inositol 1,4,5-trisphosphate receptors (IP$_{3}$Rs) are briefly reviewed. All three subtypes of IP$_{3}$R are phosphorylated by cAMP-dependent protein kinase (PKA). This potentiates IP$_{3}$-evoked Ca$^{2+}$ release through IP3R1 and IP3R2, but probably has little effect on IP$_{3}$R3. In addition, cAMP can directly sensitize all three IP$_{3}$R subtypes to IP$_{3}$. The high concentrations of cAMP required for this PKA-independent modulation of IP$_{3}$Rs is delivered to them within signalling junctions that include type 6 adenylyl cyclase and IP$_{3}$R2.