Adenosine and Propentofylline Inhibit the Proliferation of Cultured Microglial Cells

Propentofylline is a xanthine derivative that has been known to protec t neurons against ischemia-induced damage. To assess its neuroprotective mechanisms, we examined the effect of propentofylline on microglial proliferation that is thought to play an important role in neuronal damage. We determined the proliferation of microglia cultured from neonatal rat brains by measuring [3H]thymidine update. Propentofylline inhibited microglial proliferation in a dose dependent manner; EC50 was about 3 mu M. Similar results were observed with 2-chloroadenosine (agonist for A1 and A2 adenosine receptors) and 2-chloro-N6-cyclopentyladenosine (A1 receptor agonist) but not with 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethyl-carboxamidoadenosine hydrochloride (A2 receptor agonist). However, 8-cyclopentyl-1,3-dipropylxathine (A1 receptor antagonist) could not reverse the inhibitory effect of propentofylline. Our results suggest that the neuroprotection by propentofylline is, as least in part, due to the direct effect of the drug on microglia and that the drug inhibits the proliferation via a certain mechanism not directly mediated by adenosine receptors.