Extracellular NAD(+) induces a rise in [Ca(2+)](i) in activated human monocytes via engagement of P2Y(1) and P2Y(11) receptors.
Extracellular nicotinamide adenine dinucleotide (NAD(+)) is known to increase the intracellular calcium concentration [Ca(2+)](i) in different cell types and by various mechanisms. Here we show that NAD(+) triggers a transient rise in [Ca(2+)](i) in human monocytes activated with lipopolysaccharide (LPS), which is caused by a release of Ca(2+) from IP(3)-responsive intracellular stores and an influx of extracellular Ca(2+). By the use of P2 receptor-selective agonists and antagonists we demonstrate that P2 receptors play a role in the NAD(+)-induced calcium response in activated monocytes. Of the two subclasses of P2 receptors (P2X and P2Y) the P2Y receptors were considered the most likely candidates, since they share calcium signaling properties with NAD(+). The identification of P2Y(1) and P2Y(11) as receptor subtypes responsible for the NAD(+)-triggered increase in [Ca(2+)](i) was supported by several lines of evidence. First, specific P2Y(1) and P2Y(11) receptor antagonists inhibited the NAD(+)-induced increase in [Ca(2+)](i). Second, NAD(+) was shown to potently induce calcium signals in cells transfected with either subtype, whereas untransfected cells were unresponsive. Third, NAD(+) caused an increase in [cAMP](i), prevented by the P2Y(11) receptor-specific antagonist NF157.
Klein
Carina
C
Institute of Biology II, Dept. of Immunobiology, University of Leipzig, Talstrasse 33, 04103 Leipzig, Germany.
Grahnert
Anja
A
Abdelrahman
Aliaa
A
Müller
Christa E
CE
Hauschildt
Sunna
S
D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology*; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009243:NAD / Q000378:metabolism* / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1
D008070:Lipopolysaccharides; C546382:P2RY1 protein, human; C109734:P2RY11 protein, human; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D009243:NAD; D000242:Cyclic AMP; D002118:Calcium