Activation and inactivation of Ca2+ release by NAADP+.
Nicotinic acid adenine dinucleotide phosphate (NAADP+) is a recently identified metabolite of NADP+ that is as potent as inositol trisphosphate (IP3) and cyclic ADP-ribose (cADPR) in mobilizing intracellular Ca2+ 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 Ca2+ release activated by NAADP+ and the Ca2+ stores it acts on are different from those of IP3 and cADPR. In this study we show that photolyzing caged NAADP+ in intact sea urchin eggs elicits long term Ca2+ oscillations. On the other hand, uncaging threshold amounts of NAADP+ produces desensitization. In microsomes, this self-inactivation mechanism exhibits concentration and time dependence. Binding studies show that the NAADP+ receptor is distinct from that of cADPR, and at subthreshold concentrations, NAADP+ can fully inactivate subsequent binding to the receptor in a time-dependent manner. Thus, the NAADP+-sensitive Ca2+ release process has novel regulatory characteristics, which are distinguishable from Ca2+ release mediated by either IP3 or cADPR. This battery of release mechanisms may provide the necessary versatility for cells to respond to diverse signals that lead to Ca2+ mobilization.
Aarhus
R
R
Department of Physiology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Dickey
D M
DM
Graeff
R M
RM
Gee
K R
KR
Walseth
T F
TF
Lee
H C
HC
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002451:Cell Compartmentation; D008861:Microsomes / Q000378:metabolism; D009249:NADP / Q000031:analogs & derivatives* / Q000378:metabolism*; D010063:Ovum; D012617:Sea Urchins
D009249:NADP; C024376:NAADP; D002118:Calcium