Emerging role of cyclic ADP-ribose (cADPR) in smooth muscle

Cyclic adenosine diphosphate ribose (cADPR) is a naturally occurring cyclic nucleotide and represents a novel class of endogenous Ca2+ messengers implicated in the regulation of the gating properties of ryanodine receptors (RyRs). This action of cADPR occurs independently from the inositol-1,4,5-trisphosphate (IP3) receptor. The regulation of intracellular Ca2+ release is a fundamental element of cellular Ca2+ homeostasis since a number of smooth muscle functions (tone, proliferation, apoptosis, and gene expression) are modulated by intracellular Ca2+ concentration ([Ca2+]i). There has been a surge in the efforts aimed at understanding the mechanisms of cADPR-mediated Ca2+ mobilization and its impact on smooth muscle function. This review summarizes the proposed roles of cADPR in the regulation of smooth muscle tone.