Regulation of IP3 receptors by cyclic AMP

- Inositol 1,4,5-trisphosphate receptors (IP3Rs) are modulated by cAMP.
- Phosphorylation by cAMP-dependent protein kinase (PKA) potentiates IP3-evoked Ca2+ release through IP3R1 and IP3R2.
- Delivery of cAMP to IP3R2s within signalling junctions directly potentiates their responses to IP3.

Ca2+ and cAMP are ubiquitous intracellular messengers and interactions between them are commonplace. Here the effects of cAMP on inositol 1,4,5-trisphosphate receptors (IP3Rs) are briefly reviewed. All three subtypes of IP3R are phosphorylated by cAMP-dependent protein kinase (PKA). This potentiates IP3-evoked Ca2+ release through IP3R1 and IP3R2, but probably has little effect on IP3R3. In addition, cAMP can directly sensitize all three IP3R subtypes to IP3. The high concentrations of cAMP required for this PKA-independent modulation of IP3Rs is delivered to them within signalling junctions that include type 6 adenylyl cyclase and IP3R2.

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