WOUND-HEALING IS ACCELERATED BY AGONISTS OF ADENOSINE A(2) (G(ALPHA-S)-LINKED) RECEPTORS

The complete healing of wounds is the final step in a highly regulated response to injury. Although many oi the molecular mediators and cell ular events of healing are known, their manipulation for the enhanceme nt and acceleration of wound closure has not proven practical as yet. We and others have established that adenosine is a potent regulator of the inflammatory response, which is a component of wound healing. We now report that Ligation of the G(as)-linked adenosine receptors on th e cells of an artificial wound dramatically alters the kinetics of wou nd closure. Excisional wound closure in normal, healthy mice was signi ficantly accelerated by topical application of the specific A(2A) rece ptor agonist CGS-21680 (50% closure by day 2 in A(2) receptor antagoni sts. In rats rendered diabetic (streptozotocin-induced diabetes mellit us) wound healing was impaired as compared to nondiabetic rats; CGS-21 680 significantly increased the rate of wound healing in both nondiabe tic and diabetic rats. Indeed, the rate of wound healing in the CGS-21 680-treated diabetic rats was greater than or equal to that observed i n untreated normal rats. These results appear to constitute the first evidence that a small molecule, such as an adenosine receptor agonist, accelerates wound healing in both normal animals and in animals with impaired wound healing.