Activation and Inactivation of Ca
Release by NAADP
(*)
- Robert Aarhus(1),
- Deborah M. Dickey(2)(§),
- Richard M. Graeff(1),
- Kyle R. Gee(3),
- Timothy F. Walseth(2) and
- Hon Cheung Lee(1)(¶)
- From the (1)Departments of Physiology and
- (2)Pharmacology, University of Minnesota, Minneapolis, Minnesota 55455 and
- (3)Molecular Probes, Inc., Eugene, Oregon 97402
- ¶ To whom correspondence should be addressed: Dept. of Physiology, 6-255 Millard Hall, University of Minnesota, Minneapolis, MN 55455. Tel.: 612-625-7120; Fax: 612-625-0991; leehc{at}maroon.tc.umn.edu.
Abstract
Nicotinic acid adenine dinucleotide phosphate (NAADP
) is a recently identified metabolite of NADP
that is as potent as inositol trisphosphate (IP
) 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 Ca
release activated by NAADP
and the Ca
stores it acts on are different from those of IP
and cADPR. In this study we show that photolyzing caged NAADP
in intact sea urchin eggs elicits long term Ca
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 Ca
release process has novel regulatory characteristics, which are distinguishable from Ca
release mediated by either IP
or cADPR. This battery of release mechanisms may provide the necessary versatility for cells to respond to diverse signals
that lead to Ca
mobilization.
Footnotes
-
↵§ Supported by National Institutes of Health Training Grant T32GM07994.
-
↵* This work was supported by National Institutes of Health Grants HD32040 (to H. C. L.) and DA08131 (to T. F. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- IP
-
inositol trisphosphate
- cADPR
-
cyclic ADP-ribose
- NAADP
-
nicotinic acid adenine dinucleotide.
- IP
-
- Received February 8, 1996.
- Revision received February 19, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
