Effects of PCB 84 enantiomers on [3H]-phorbol ester binding in rat cerebellar granule cells and 45Ca2+-uptake in rat cerebellum.
There is evidence that polychlorinated biphenyl (PCB) congeners with ortho chlorine substituents have potential to cause neurotoxicity. Many PCB congeners implicated in these neurotoxic effects are chiral. It is currently unknown if the enantiomers of chiral PCB congeners have different neurotoxic effects. We herein report the effect of racemic 2,2',3,3',6-pentachlorobiphenyl (PCB 84) and its enantiomers on two neurochemical measures, protein kinase C (PKC) translocation as determined by [3H]-phorobol ester binding in cerebellar granule cells and Ca2+-sequestration as determined by 45Ca2+-uptake by microsomes isolated from adult rat cerebellum. Both (+)- and (-)-PCB 84 increased [3H]-phorobol ester binding in a concentration-dependent manner with (-)-PCB 84 being slightly more potent. Racemic PCB 84 was significantly more potent and efficacious than the pure enantiomers alone. (-)- and (+)-PCB 84 each inhibited microsomal 45Ca2+-uptake to a similar extent, whereas racemic PCB 84 was more potent and efficacious. These results indicate that PCB 84 enantiomers alone can have different potencies, and these may differ from that of the racemic mixture, observations that may have important implications for understanding the mechanisms of neurotoxicity of chiral PCB congeners.
Lehmler
Hans-Joachim
HJ
Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, 100 Oakdale Campus, #124 IREH, Iowa City, IA 52242-5000, USA. hans-joachim-lehmler@uiowa.edu
Robertson
Larry W
LW
Garrison
A Wayne
AW
Kodavanti
Prasada Rao S
PR
D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics*; D002132:Calcium Radioisotopes; D002462:Cell Membrane / Q000201:enzymology; D002531:Cerebellum / Q000187:drug effects* / Q000201:enzymology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D005260:Female; D008297:Male; D008861:Microsomes / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013237:Stereoisomerism
D002132:Calcium Radioisotopes; D015240:Phorbol 12,13-Dibutyrate; D011078:Polychlorinated Biphenyls; D011493:Protein Kinase C; D002118:Calcium