Adenosine acts as a chemoprotective agent by stimulating G-CSF production:A role for Al and A3 adenosine receptors

Adenosine, a ubiquitous nucleoside, is released into the extracellular envi ronment from metabolically active or stressed cells. It binds to cells thro ugh specific A(1), A(2A), A(2B), and A3 G-protein-associated cell-surface r eceptors, thus acting as a signal-transduction molecule by regulating the l evels of adenylyl cyclase and phospholipase C. in this study, we showed tha t adenosine stimulates the proliferation of murine bone marrow cells in vit ro. Pharmacological studies, using antagonists to the adenosine receptors, revealed that this activity was mediated through the binding of adenosine t o its A1 and A3 receptors. This result was further corroborated by showing that the two selective Al and A3 receptor agonists, N-cyclopentyladenosine (CPA) and 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methy l-beta-D-ribofuranuronamide (IB-MECA) respectively. induced bone marrow cel l proliferation in a manner similar to adenosine. Adenosine's interaction w ith its A1 and A3 receptors induced G-CSF production, which led to its stim ulatory effect on bone marrow cells. These results were confirmed in vivo w hen we demonstrated that low-dose adenosine (0.25 mg/kg) acted as a chemopr otective agent. When administered after chemotherapy, it restored the numbe r of leukocytes and neutrophils to normal levels, compared with the decline in these parameters after chemotherapy alone. it is suggested that low-dos e adenosine, already in clinical use, may also be applied as a chemoprotect ive agent, J. Cell. Physiol. 183:393-398, 2000. (C) 2000 Wiley-Liss, Inc.