Abstracts (complete list) - Wissenschaft Online

Anja Grahnert, Erik Schilling, Carina Klein, Sunna Hauschildt
Extracellular NAD + triggers transient [Ca 2+ ] i changes in
human monocytes
via P2X-receptors
Recently extracellular NAD + has been identified as a stimulus capable of inducing a rise
in [Ca 2+ ] i in different cell types by different mechanism. In this study we could show
that NAD + leads to a transient increase in [Ca 2+ ] i in human monocytes mediated by an
influx of [Ca 2+ ] i from the extracellular medium. As NAD + does not exert its effect by
entering the cells and as ATP prevents the NAD + induced effect we investigated the
involvement of ATP receptors in the Ca2+ -response. ATP receptors are P2 purinoceptors
classified into ionotropic P2X and metabotropic, G-protein-coupled P2Y receptors. P2Y
receptors can be excluded, because NAD + only leads to an influx of extracellular Ca2+ .
Of the seven P2X receptors P2X1 , P2X4 , and P2X7 were found to be expressed on
human monocytes. The involvement of P2X1 as a receptor subtype mediating the effect
of NAD + is supported by the finding that the increase in [Ca2+ ] i is inhibited by the
specific P2X1 antagonists NF449 and suramin. Furthermore P2X7 plays a role by the NAD
+ -induced increase in [Ca2+ ]i . The P2X7 antagonist KN62 and an anti- P2X7-Ab block
the NAD + effect.
Surprisingly the binding of the P2X7 receptor did not lead to a pore formation. These
data show for the first time that extracellular NAD + acts as a ligand at P2X receptors of
human monocytes.