Klinisk Biokemi i Norden · 4 2016
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and Osteoporosis. By using murine P2X7 knockout
models and examine human genetic variants of this
receptor, their research helped reveal part of the role
that P2X7 plays in osteoblasts, osteoclasts and osteo-
cytes [11–13]. As a final example of studies on ATP
receptors, researchers at Glostrup Research Institute
have shown that P2Y
2
is important for endothelial-
dependent relaxation of mouse coronary vessels [14].
The breadth of research on ATP receptors des-
cribed above witnesses a research field with broad
prospects [15–19]. The flowering of this research is
largely taken as a result of the realization that ATP
besides being an important energy carrier was finally
recognized as important signalling molecule. Now
that ATP is accepted as an extracellular signalling
molecule, this has formed the basis of a whole new
research field of purinergic receptor signalling. With
the emergence nucleotides as extracellular transmit-
ters comes also the potential for therapeutic targets.
An example is anti-cancer treatment with herb
extract Chrysophanic that functions by reducing the
level of ATP [20]. As the understanding of ATP as an
extracellular transmitter increases, the list of drugs
that interfere with ATP signalling is likely to expand
in the future.
Reference list
1. Di Virgilio F. Liaisons dangereuses: P2X(7)
and the inflammasome. Trends Pharmacol
Sci 2007;28:465–72.
2. Swennen EL, Dagnelie PC, Van den Beucken T,
Bast A. Radioprotective effects of ATP in
human blood ex vivo. Biochem Biophys Res
Commun 2008;367:383–7.
3. Fink SL, Cookson BT. Pyroptosis and host cell
death responses during Salmonella infection.
Cell Microbiol 2007;9:2562–70.
4. Leal Denis MF, Alvarez HA, Lauri N, et al.
Dynamic regulation of cell volume and extra-
cellular ATP of human erythrocytes. PLoS
One 2016;11:e0158305. doi: 10.1371/journal.
pone.0158305
5. Sandilos JK, Chiu Y-H, Chekeni FB, et al.
Pannexin 1, an ATP release channel, is activa-
ted by caspase cleavage of its pore-associa-
ted C-terminal autoinhibitory region. J Biol
Chem 2012; 287:11303–11.
6. Locovei S, Bao L, Dahl G. Pannexin 1 in
erythrocytes: function without a gap. Proc
Natl Acad Sci U S A 2006;103:7655–9.
7. Dahl G. ATP release through pannexon chan-
nels. Philos Trans R Soc Lond B Biol Sci.2016;
doi: 10.1098/rstb.2014.0191
Figure 1: ATP acts as an extra-
cellular signalling molecule.
ATP can be released from cells
to the extracellular space via
several mechanisms, including
exocytosis and rupture of the
cell membrane. ATP receptors
are ubiquitously expressed in the
body and comprise P2Y receptors
(seven-transmembrane) and P2X
(ion channels). These receptors
control various pathways which
are found implicated in diverse
disorders, such as P2Y
11
in nar-
colepsy and P2X7 in osteoporosis
(see text for details).
