Activation and inactivation of Ca 2+ release by NAADP +

Abstract

Nicotinic acid adenine dinucleotide phosphate (NAADP +) is a recently identified metabolite of NADP + that is as potent as inositol trisphosphate (IP 3) and cyclic ADP-ribose (cADPR) in mobilizing intracellular Ca 2+ in sea urchin eggs and microsomes (Clapper, D. L., Walseth, T. F., Dargie, P. J., and Lee, H. C. (1987) J. Biol. Chem. 262, 9561-9568; Lee, H. C., and Aarhus, R. (1995) J. Biol. Chem. 270, 2152-2157). The mechanism of Ca 2+ release activated by NAADP + and the Ca 2+ stores it acts on are different from those of IP 3 and cADPR. In this study we show that photolyzing caged NAADP + in intact sea urchin eggs elicits long term Ca 2+ oscillations. On the other hand, uncaging threshold amounts of NAADP + produces desensitization. In microsomes, this self-inactivation mechanism exhibits concentration and time dependance. Binding studies show that the NAADP + recaptor is distinct from that of cADPR, and at subthreshold concentrations, NAADP + can fully inactirate subsequent binding to the receptor in a time- dependent manner. Thus, the NAADP +-sensitive Ca 2+ release process has novel regulatory characteristics, which are distinguishable from Ca 2+ release mediated by either IP 3 or cADPR. This battery of release mechanisms may provide the necessary versatility for cells to respond to diverse signals that lead to Ca 2+ mobilization.