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 neuroprotecti ve mechanisms, we examined the effect of propentofylline on microglial proliferation that is thought to play an important role in neuronal d amage. We determined the proliferation of microglia cultured from neon atal rat brains by measuring [H-3]thymidine uptake. Propentofylline in hibited microglial proliferation in a dose dependent manner; EC(50) wa s about 3 mu M. Similar results were observed with 2-chloroadenosine ( agonist for A1 and A2 adenosine receptors) and 2-chloro-N-6-cyclopenty ladenosine (A1 receptor agonist) but not with thyl)phenethylamino-5'-N -ethylcarboxamidoadenosine hydrochloride (A2 receptor agonist). Howeve r, 8-cyclopentyl-1,3-dipropylxathine (A1 receptor antagonist) could no t reverse the inhibitory effect of propentofylline. Our results sugges t that the neuroprotection by propentofylline is, at least in part, du e to the direct effect of the drug on microglia and that the drug inhi bits the proliferation via a certain mechanism not directly mediated b y adenosine receptors. (C) 1996 Academic Press, Inc.