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-[3H]aspartate release were unchanged upon treatment with adenosine or the selective A1 receptor agonists, N6-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-[3H]aspartate release. Since the effect of MeHg on D-[3H]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 A1 agonists CPA and CHP, and the adenosine antagonist, theophylline, on astrocytic [GSH]i. Attenuation of the stimulatory effect of MeHg on D-[3H]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-[3H]aspartate release is not known, the data suggest a role for adenosine in its regulation.
Aschner
M
M
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1083, USA.
Mullaney
K J
KJ
Wagoner
D E
DE
Lash
L H
LH
Kimelberg
H K
HK
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008767:Methylmercury Compounds / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D013806:Theophylline / Q000494:pharmacology; D014316:Tritium
D008767:Methylmercury Compounds; D018047:Receptors, Purinergic P1; D014316:Tritium; D001224:Aspartic Acid; D018698:Glutamic Acid; D013806:Theophylline; D005978:Glutathione; D000241:Adenosine; C004925:methylmercuric chloride