Activation and inactivation of Ca2+ release by NAADP+

Robert Aarhus, Deborah M Dickey, Richard M Graeff, Kyle R. Gee, Timothy F Walseth, Hon Cheung Lee

Research output: Contribution to journalArticle

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Abstract

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 sub threshold 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.

Original languageEnglish (US)
Pages (from-to)8513-8516
Number of pages4
JournalJournal of Biological Chemistry
Volume271
Issue number15
DOIs
StatePublished - Apr 12 1996

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Chemical activation
Cyclic ADP-Ribose
Sea Urchins
Microsomes
Eggs
NAADP
Inositol
Metabolites
NADP

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Activation and inactivation of Ca2+ release by NAADP+. / Aarhus, Robert; Dickey, Deborah M; Graeff, Richard M; Gee, Kyle R.; Walseth, Timothy F; Lee, Hon Cheung.

In: Journal of Biological Chemistry, Vol. 271, No. 15, 12.04.1996, p. 8513-8516.

Research output: Contribution to journalArticle

Aarhus, Robert ; Dickey, Deborah M ; Graeff, Richard M ; Gee, Kyle R. ; Walseth, Timothy F ; Lee, Hon Cheung. / Activation and inactivation of Ca2+ release by NAADP+. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 15. pp. 8513-8516.
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