Ca2+ ions play a critical role in the biochemical cascade of signal transduction pathways, leading to the activation of immune cells. In the present study, we show that the exposure of freshly isolated human monocytes to NAD+ results in a rapid concentration-dependent elevation of [Ca2+]i (intracellular free Ca2+ concentration) caused by the influx of extracellular Ca2+. NAD+ derivatives containing a modified adenine or nicotinamide ring failed to trigger a Ca2+ increase. Treating monocytes with ADPR (ADP-ribose), a major degradation product of NAD+, also resulted in a rise in [Ca2+]i. Selective inhibition of CD38, an NAD-glycohydrolase that generates free ADPR from NAD+, does not abolish the effect of NAD+, excluding the possibility that NAD+ might act via ADPR. The NAD+-induced Ca2+ response was prevented by the prior addition of ADPR and vice versa, indicating that both compounds share some mechanisms mediating the rise in [Ca2+]i. NAD+, as well as ADPR, were ineffective when applied following ATP, suggesting that ATP controls events that intersect with NAD+ and ADPR signalling.
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Research Article|
September 07 2004
Extracellular NAD+ regulates intracellular free calcium concentration in human monocytes
Anja GERTH;
Anja GERTH
*Department of Immunobiology, Institute of Zoology, University of Leipzig, Liebigstrasse 18, D-04103 Leipzig, Germany
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Karen NIEBER;
Karen NIEBER
†Department of Pharmacology for Natural Sciences, Institute of Pharmacy, University of Leipzig, Liebigstrasse 18, D-04103 Leipzig, Germany
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Norman J. OPPENHEIMER;
Norman J. OPPENHEIMER
‡Department of Pharmaceutical Chemistry S-926, University of California, San Francisco, CA 94143-0446, U.S.A.
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Sunna HAUSCHILDT
Sunna HAUSCHILDT
1
*Department of Immunobiology, Institute of Zoology, University of Leipzig, Liebigstrasse 18, D-04103 Leipzig, Germany
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
June 09 2004
Revision Received:
June 30 2004
Accepted:
July 02 2004
Accepted Manuscript online:
July 02 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2004
Biochem J (2004) 382 (3): 849–856.
Article history
Received:
June 09 2004
Revision Received:
June 30 2004
Accepted:
July 02 2004
Accepted Manuscript online:
July 02 2004
Connected Content
A commentary has been published:
NAD+ surfaces again
Citation
Anja GERTH, Karen NIEBER, Norman J. OPPENHEIMER, Sunna HAUSCHILDT; Extracellular NAD+ regulates intracellular free calcium concentration in human monocytes. Biochem J 15 September 2004; 382 (3): 849–856. doi: https://doi.org/10.1042/BJ20040979
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