SENSITIVITY OF ADENOSINE TRIPHOSPHATASES IN DIFFERENT BRAIN-REGIONS TO POLYCHLORINATED BIPHENYL CONGENERS

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 st udy compared the in vitro effects of a putative neuroactive ortho-biph enyl (2,2'-dichlorobiphenyl; DCBP) with that of a putative non-neuroac tive congener lacking ortho-chlorine substitutions (3,3',4,4',5-pentac hlorobiphenyl; PCBP) on Mg2+-ATPase activity in mitochondrial and syna ptosomal preparations from striatum, hypothalamus, cerebellum and hipp ocampus. In these studies, DCBP significantly inhibited oligomycin-sen sitive (OS) Mg2+-ATPase activity in all four brain regions in a concen tration-dependent manner; PCBP, on the other hand, had no effect on OS Mg2+-ATPase activity in any brain region examined at concentrations u p to 100 mu M. The striatum, a dopamine-rich region, was not preferent ially sensitive to the effects of DCBP. Furthermore, DCBP did not inhi bit synaptosomal Na+/ K+-ATPase activity, suggesting a specificity of action on OS Mg2+-ATPase. These data support previous structure-activi ty 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 ne uroactivity of ortho-chlorinated PCBs.