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 Ca(2+) 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 (IP(3)) receptor. The regulation of intracellular Ca(2+) release is a fundamental element of cellular Ca(2+) homeostasis since a number of smooth muscle functions (tone, proliferation, apoptosis, and gene expression) are modulated by intracellular Ca(2+) concentration ([Ca(2+)](i)). There has been a surge in the efforts aimed at understanding the mechanisms of cADPR-mediated Ca(2+) mobilization and its impact on smooth muscle function. This review summarizes the proposed roles of cADPR in the regulation of smooth muscle tone.