Animal studies of the topical application of
adenosine A2A receptor agonists show that it promotes
wound closure. To further confirm the efficacy of
adenosine A2A receptor agonists as promoters of wound healing, we compared the effect of
MRE0094, a novel selective
adenosine A2A receptor agonist, to CGS-21680, a reference selective
adenosine A2A receptor agonist, as well as to recombinant human
platelet-derived growth factor (0.01%
Becaplermin gel), an agent currently used to promote healing of diabetic
ulcers, on
wound closure in healthy BALB/C mice.
Wounds (approximately 12 mm diameter) were created on the dorsum of mice (two per mouse) and then treated daily with vehicle, 0.01%
Becaplermin gel, or different doses of the
adenosine A2A receptor agonists. The
wound margins were traced onto
plastic sheets, and the
wound areas were digitized, quantitated, and compared. We found that application of
MRE0094 (1 microg/
wound and 10 microg/
wound) and CGS-21680 (1 microg/
wound and 5 microg/
wound) achieved 50%
wound closure significantly more rapidly than control application (day 1.9, 1.9, 3.5, 3.2, respectively, versus control day 4, p < 0.05 ANOVA). Surprisingly, neither higher nor lower concentrations of CGS-21680 affected the rate of
wound closure, as compared to control. In contrast,
Becaplermin gel did not increase the rate at which
wounds closed (50% closure by day 7.2, p = NS versus control). These data confirm our prior observations that
adenosine A2A receptor agonists promote
wound closure, and they suggest that these agents may be as effective if not more effective than
Becaplermin gel for the treatment of poorly healing
wounds.