Sensitivity of adenosine triphosphatases in different brain regions to polychlorinated biphenyl congeners

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Abstract
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 (2,2′‐dichlorobiphenyl; DCBP) with that of a putative non‐neuroactive congener lacking ortho‐chlorine substitutions (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 μM. The striatum, a dopamine‐rich region, was not preferentially sensitive to the effects of DCBP. 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 neuroactivity of ortho‐chlorinated PCBs.