Cyclic ADP-ribose as a second messenger revisited from a new aspect of signal transduction from receptors to ADP-ribosyl cyclase

Cyclic ADP-ribose (cADPR), an endogenous modulator of ryanodine receptor Ca 2+ -releasing channels, is found in various tissues. Cytosolic injection of cADPR induces an elevation of intracellular Ca2+ concentrations or potenti ates Ca2+ increases. cADPR facilitates neurotransmitter or insulin release and modifies ionic currents. cADPR is synthesized by ADP-ribosyl cyclase an d is metabolized by cADPR hydrolase. ADP-ribosyl cyclase activity is up-reg ulated by nitric oxide/cyclic GMP-dependent phosphorylation or receptor sti mulation via G-proteins within membranes. These findings suggest that cADPR is a second messenger in cellular Ca2+ signaling. However, many intriguing issues remain to be addressed before this identity is confirmed. (C) 2001 Elsevier Science Inc. All rights reserved.