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 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 Mg(2+)-ATPase activity in mitochondrial and synaptosomal preparations from striatum, hypothalamus, cerebellum and hippocampus. In these studies, DCBP significantly inhibited oligomycin-sensitive (OS) Mg(2+)-ATPase activity in all four brain regions in a concentration-dependent manner; PCBP, on the other hand, had no effect on OS Mg(2+)-ATPase activity in any brain region examined at concentrations up to 100 microM. 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 Mg(2+)-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.
Maier
W E
WE
Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC 27599.
Kodavanti
P R
PR
Harry
G J
GJ
Tilson
H A
HA
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D006180:Proton-Translocating ATPases / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
C012280:2,2'-dichlorobiphenyl; D011078:Polychlorinated Biphenyls; D006180:Proton-Translocating ATPases; C023035:3,4,5,3',4'-pentachlorobiphenyl