Adenosine modulates methylmercuric chloride (MeHgCl)-induced d-aspartate release from neonatal rat primary astrocyte cultures

• Published in: Brain research Vol. 689; no. 1; pp. 1 - 8
• Main Authors: Aschner, M., Mullaney, K.J., Wagoner, D.E., Lash, L.H., Kimelberg, H.K.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 14.08.1995; Amsterdam Elsevier; New York, NY
• Subjects: Adenosine - analogs & derivatives; Adenosine - pharmacology; Analysis of Variance; Animals; Animals, Newborn; Aspartate; Aspartic Acid - metabolism; Astrocyte; Astrocytes - drug effects; Astrocytes - metabolism; Biological and medical sciences; Cells, Cultured; Glutamate; Glutamic Acid - metabolism; Glutathione; Glutathione - metabolism; Medical sciences; Methylmercury; Methylmercury Compounds - antagonists & inhibitors; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Rat; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P1 - drug effects; Theophylline - pharmacology; Tritium; Aspartate; Astrocyte; Rat; Glutamate; Methylmercury; Glutathione; Adenosine; Neuroglia; Rodentia; Neuroprotective agent; In vitro; Heavy metal; Vertebrata; Mammalia; Animal; Excitatory aminoacid; Neurotransmitter; Adenosine receptor; Release
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(95)00496-D

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 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-[ 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 A 1 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.