Choksi NY, Waller CL, Booth RG. Neurotoxic and neuroprotective effects of polychlorinated biphenyls and adenosine compounds in rat brain. Presented at Society for Neuroscience Annual Meeting, San Diego, CA, November 1995
Loss of dopaminergic cells in the substantia nigra decreases dopamine (DA) concentration in the striatum and produces the main symptoms of Parkinson s disease. Although the etiology of Parkinson’s disease is unknown, environmental factors are proposed to play a role in development of the disease. Polychlorinated biphenyls (PCBs) are widespread in the environment and have been shown to cause central and peripheral toxic effects in humans and animals. We report that several PCBs inhibit tyrosine hydroxylase (TH) activity and DA synthesis in rat striatum in vitro (IC50 * 150-200 pM). In contrast to the inhibition of TH activity by PCBs, we have observed that TH activity and DA synthesis in striatal tissue is stimulated by activation of adenosine A2 receptors. We report that 2-phenylaminoadenosine (2-PAD) stimulates TH activity and DA synthesis in rat striatum in vitro (EC50 = 10 pM) through an A2 receptor mechanism. 2-PAD also stimulates DA synthesis in rat striatum in vivo (ED50 * 0.6pmoles/kg) after intracerebroventricular injection. These results suggest that A2 ligands may attenuate PCB induced inhibition of TH activity and DA synthesis. We propose that PCBs, present as contaminants in the environment, may be dopaminergic neurotoxicants and may play a role in the etiology of Parkinson’s disease. Furthermore, we propose that adenosine receptor mechanisms may play a neuroprotective role to modulate PCB-induced dopaminergic neurotoxicity.