ADENOSINE MODULATES METHYLMERCURIC CHLORIDE (MEHGCL)-INDUCED D-ASPARTATE RELEASE FROM NEONATAL RAT PRIMARY ASTROCYTE CULTURES

The effects of adenosine, and selective adenosine receptor agonists and antagonists on methylmercury (MeHg)-induced aspartate release were studied in neonatal rat primary astrocyte cultures. Whereas basal levels of D-[H-3]aspartate release were unchanged upon treatment with adenosine or the selective A(1) receptor agonists, N-6-cyclopentyladenosine (CPA), cyclohexyladenosine (CHA), and R-phenylisopropyladenosine (R-PIA), all partially reversed the MeHg-induced release of D-aspartate. Treatment of astrocytes with the xanthine derivative, theophylline, an adenosine antagonist, reversed the inhibitory effect of adenosine on MeHg-induced D-[H-3]aspartate release. Since the effect of MeHg on D-[H-3]aspartate release is known to be associated with sulfhydryl (-SH) groups which are controlled by intracellular glutathione concentrations [GSH]I, we also evaluated the effects of adenosine, the A(1) agonists CPA and CHP, and the adenosine antagonist, theophylline, on astrocytic [GSH](i). Attenuation of the stimulatory effect of MeHg on D-[H-3]aspartate release by adenosine and its agonists occurred in the presence of reduced astrocytic [GSH](i), suggesting that other mechanisms must be invoked for this protective effect. Whilst the mechanism of MeHg-induced D-[H-3]aspartate release is not known, the data suggest a role for adenosine in its regulation.