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Published online 7 August 2000. doi:10.1083/jcb.150.3.581
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© The Rockefeller University Press, 0021-9525/2000//581 $5.00
The Journal of Cell Biology, Volume 150, Number 3, , 2000 581-588

Original Article

Nicotinic Acid Adenine Dinucleotide Phosphate (Naadp+) Is an Essential Regulator of T-Lymphocyte Ca2+-Signaling



Ingeborg Berga, Barry V.L. Potterb, Georg W. Mayra, and Andreas H. Gusea

a Institute of Medical Biochemistry and Molecular Biology, Division of Cellular Signal Transduction, University of Hamburg, D-20146 Hamburg, Germany
b Wolfson Laboratory for Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom
University of Hamburg, Institute for Medical Biochemistry and Molecular Biology, Div. Cellular Signal Transduction, Grindelallee 117, IV, D-20146 Hamburg, Germany.49-40-42838-427549-40-42838-4276

guse{at}uke.uni-hamburg.de

Microinjection of human Jurkat T-lymphocytes with nicotinic acid adenine dinucleotide phosphate (NAADP+) dose-dependently stimulated intracellular Ca2+-signaling. At a concentration of 10 nM NAADP+ evoked repetitive and long-lasting Ca2+-oscillations of low amplitude, whereas at 50 and 100 nM, a rapid and high initial Ca2+-peak followed by trains of smaller Ca2+-oscillations was observed. Higher concentrations of NAADP+ (1 and 10 µM) gradually reduced the initial Ca2+-peak, and a complete self-inactivation of Ca2+-signals was seen at 100 µM. The effect of NAADP+ was specific as it was not observed with nicotinamide adenine dinucleotide phosphate. Both inositol 1,4,5-trisphosphate– and cyclic adenosine diphosphoribose–mediated Ca2+-signaling were efficiently inhibited by coinjection of a self-inactivating concentration of NAADP+. Most importantly, microinjection of a self-inactivating concentration of NAADP+ completely abolished subsequent stimulation of Ca2+-signaling via the T cell receptor/CD3 complex, indicating that a functional NAADP+ Ca2+-release system is essential for T-lymphocyte Ca2+-signaling.

Key Words: cyclic ADP-ribose • inositol 1,4,5-trisphosphate • T cell activation • signal transduction • ryanodine receptor

© 2000 The Rockefeller University Press

Abbreviations used in this paper: [Ca2+]i, intracellular Ca2+ concentration; cADPR, cyclic ADP-ribose; Ins(1,4,5)P3, D-myo-inositol 1,4,5-trisphosphate; InsP3-R, Ins(1,4,5)P3 receptor; Ins(1,4,6)PS3, D-myo-inositol 1,4,6-trisphosphorothioate; NAADP+, nicotinic acid adenine dinucleotide phosphate; NADP+, nicotinamide adenine dinucleotide phosphate; RyR, ryanodine receptor(s); TCR/CD3, T cell receptor/CD3.


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