Effects of PCB 84 enantiomers on [3H]-phorbol ester binding in rat cerebellar granule cells and 45Ca2+-uptake in rat cerebellum

Hans-Joachim Lehmler; Larry W Robertson; A Wayne Garrison; Prasada Rao S Kodavanti

doi:10.1016/j.toxlet.2004.12.011

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Effects of PCB 84 enantiomers on [3H]-phorbol ester binding in rat cerebellar granule cells and 45Ca2+-uptake in rat cerebellum

Journal article

Peer reviewed

Effects of PCB 84 enantiomers on [3H]-phorbol ester binding in rat cerebellar granule cells and 45Ca2+-uptake in rat cerebellum

Hans-Joachim Lehmler, Larry W Robertson, A Wayne Garrison and Prasada Rao S Kodavanti

Toxicology letters, Vol.156(3), pp.391-400

04/28/2005

DOI: 10.1016/j.toxlet.2004.12.011

PMID: 15763638

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Abstract

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.

Microsomes - metabolism

Stereoisomerism

Cytoplasmic Granules - drug effects

Rats, Long-Evans

Cerebellum - drug effects

Rats

Male

Phorbol 12,13-Dibutyrate - pharmacology

Cerebellum - enzymology

Pregnancy

Cell Membrane - enzymology

Cytosol - enzymology

Cytoplasmic Granules - enzymology

Animals

Polychlorinated Biphenyls - toxicity

Protein Kinase C - metabolism

Calcium Radioisotopes

Female

Calcium - pharmacokinetics

Details

Title: Subtitle: Effects of PCB 84 enantiomers on [3H]-phorbol ester binding in rat cerebellar granule cells and 45Ca2+-uptake in rat cerebellum
Creators: Hans-Joachim Lehmler - 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
Larry W Robertson
A Wayne Garrison
Prasada Rao S Kodavanti
Resource Type: Journal article
Publication Details: Toxicology letters, Vol.156(3), pp.391-400
DOI: 10.1016/j.toxlet.2004.12.011
PMID: 15763638
NLM abbreviation: Toxicol Lett
ISSN: 0378-4274
eISSN: 1879-3169
Publisher: Netherlands
Grant note: P42 ES013661 / NIEHS NIH HHS ES 012475 / NIEHS NIH HHS ES 07380 / NIEHS NIH HHS
Language: English
Date published: 04/28/2005
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute
Record Identifier: 9984001083502771

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