Thursday, August 30, 2012
Figure 1. Effects of adenosine A2A
receptor agonism. Activation of the adenosine A2A receptor
known to both inhibit inflammatory processes and promote vasodilation. The cell
surface enzyme ecto-5ʹ-nucleotidase (NT5E; NT; CD73) is highly
expressed by immune cells and endothelial cells and is one of the central
regulators of endogenous adenosine signaling. CD73 dephosphorylates adenosine
monophosphate (AMP) to form adenosine.
(I) In immune cells, adenosine signaling through
ADORA2A inhibits proinflammatory processes.
(II) In endothelial cells, adenosine signaling
through ADORA2A promotes vasodilation.
In Flögel et al., researchers showed that their
ADORA2A agonist prodrug is selectively activated at sites of
inflammation, at which CD73 is highly upregulated. Thus, the molecule is able
to exert potent anti-inflammatory effects at doses that do not also cause