Extracellular guanosine increases astrocyte cAMP: inhibition by adenosine A2 antagonists

Both extracellular guanosine and adenosine stimulated astrocyte proliferation in vitro and increased intracellular cAMP 6-fold within 2 min. The effects of both guanosine and adenosine on proliferation and cAMP levels were inhibited by antagonists of adenosine A2 receptors but augmented by A1 receptor antagonists. The correlation between cAMP accumulation and stimulation of cell proliferation by adenosine and guanosine indicates that increased intracellular cAMP may be one of the second messengers involved in these effects. Guanosine is not an adenosine A2 receptor agonist and does not activate adenylate cyclase. It may exert its effects indirectly by increasing the endogenous extracellular adenosine concentration.