Calcium-induced calcium release and cyclic ADP-ribose-mediated signaling in the myocytes from small coronary arteries.

Cyclic ADP-ribose (cADPR), an endogenous metabolite of nicotinamide adenine dinucleotide, was first reported to be present in sea urchin eggs and to possess Ca mobilizing activity (Clapper et al., 1987; Lee et al., 1989). Recent studies have indicated that cADPR is produced in a variety of mammalian tissues and cells, including heart, liver, spleen, brain and red blood cells, pituitary cells, as well as renal epithelial cells (Beers et al., 1995; Koshiyama et al., 1991; Takesawa et al., 1993; White et al., 1993). Basal concentrations of cADPR in cardiac muscle, liver, and brain are estimated to be 100–200 nM (Galione, 1994; Lee, 1994). Like sea urchin eggs, cADPR also causes Ca release from the endoplasmic reticulum in these mammalian tissues and cells. It mobilizes intracellular Ca by a mechanism completely independent of inositol 1,4,5trisphosphate (IP3), since the IP3 receptor antagonist heparin cannot block the effect of cADPR (Galione,