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SENSITIVITY OF ADENOSINE TRIPHOSPHATASE IN DIFFERENT BRAIN REGIONS TO POLYCHLORINATED BIPHENYL CONGENERS
Citation:
Maier, W., P. Kodavanti, G. Harry, AND H. Tilson. SENSITIVITY OF ADENOSINE TRIPHOSPHATASE IN DIFFERENT BRAIN REGIONS TO POLYCHLORINATED BIPHENYL CONGENERS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/109, 1994.
Description:
Polychlorinated biphenyl (PCBs) mixtures contain a number of different congeners, some of which have been proposed to be neuroactive. Recent studies have suggested that ortho-substituted PCBs may be neuroactive, while "dioxin-like" non-ortho-substituted congeners are not. This study compared the in-vitro effects of a putative neuroactive ortho-biphenyl (i.e., 2,2'-dichlorobiphenyl; DCBP) with that of a putative non-neuroactive congener lacking ortho-chlorine substitutions (i.e., 3,3', 4,4', 5-pentachlorobiphenyl; PCBP) on Mg2+-ATPase activity in mitochondrial and synaptosomal preparations from striatum, hypothalamus, cerebellum and hippocampus. In these studies, DCBP significantly inhibited oligomycin-sensitive (OS) Mg2+-ATPase activity in all four brain regions in a concentration-dependent manner. PCBP, on the other hand, had no effect on OS MG2+-ATPase activity in any brain region examined at concentrations up to 100 uM. The striatum, a dopamine rich region, was not preferentially sensitive to the effects of DVBP. Furthermore, DCBP did not inhibit synaptosomal Na+/K+-ATPase activity, suggesting a specificity of action on OS Mg2+-ATPase. These data support previous structure-activity relationships suggesting that ortho-substituted PCB congeners are neuroactive, while non-ortho-substituted congeners are not. Disruption of mitochondrial oxidative energy production may play a role in the neuro-activity of ortho-chlorinated PCBs.