PMID: 8937895Nov 1, 1996Paper

Effects of chlorpyrifos on high-affinity choline uptake and [3H]hemicholinium-3 binding in rat brain

Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology
Jing Liu, Carey Pope

Abstract

High, subcutaneous doses of the organophosphorus insecticide chlorpyrifos (CPF) in adult male rats can be well-tolerated despite extensive and persistent acetylcholinesterase (AChE) inhibition. We propose that changes in acetylcholine synthesis could modulate the toxicity associated with extensive AChE inhibition following CPF exposure. High-affinity choline uptake (HACU, the rate-limiting step in acetlcholine synthesis) and binding to [3H]-hemicholinium-3 (HC-3, a specific ligand for the choline transporter) were chosen as indicators of acetylcholine synthesis. Female, Sprague-Dawley rats (220-280 g) were treated with either vehicle (peanut oil, 2 ml/kg, sc) or CPF (280 mg/kg, 2 ml/kg, sc), examined daily for clinical signs of toxicity, and sacrificed 1, 2, or 7 days later for neurochemical measurements (AChE inhibition, muscarinic receptor binding using [3H]quinuclidinyl benzilate (QNB) and [3H]cis-methyldioxolane (CD) as ligands, HACU and [3H]HC-3 binding) in frontal cortex. Despite extensive AChE inhibition (90-93%) at all time points, relatively minor degrees of overt toxicity were noted in CPF-treated rats. Binding to the non-selective muscarinic antagonist [3H]QNB was reduced (10-34%), whereas binding to the putative m2-...Continue Reading

Citations

Apr 15, 2004·Toxicology and Applied Pharmacology·Subramanya KaranthCarey Pope
Sep 15, 2001·Brain Research. Developmental Brain Research·K W RainesT A Slotkin
Mar 8, 2002·Brain Research. Developmental Brain Research·T A SlotkinF J Seidler
Dec 4, 2002·Neurotoxicology and Teratology·Edward D LevinTheodore A Slotkin
Sep 16, 2003·Neurotoxicology and Teratology·Subramanya Karanth, Carey Pope
Dec 1, 1997·Environmental Toxicology and Pharmacology·C N Pope, J Liu
Mar 13, 2008·Environmental Health Perspectives·Theodore A SlotkinFrederic J Seidler
Sep 19, 2008·Journal of Toxicology and Environmental Health. Part a·Elmar M Udarbe ZamoraCarey N Pope
Aug 24, 2011·Contrast Media & Molecular Imaging·Zhan-Yan PanHuan-Ming Xiong
Aug 30, 2008·Critical Reviews in Toxicology·David L EatonPeter S Spencer
Mar 18, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Fernando CañadasFernando Sánchez-Santed
Jan 11, 2003·Journal of Toxicology and Environmental Health. Part a·Jason Richardson, Janice Chambers
May 1, 2001·Current Protocols in Toxicology·S Padilla
Jan 1, 2004·Toxicology Mechanisms and Methods·Ramesh C Gupta
Jun 16, 2011·Toxicology and Applied Pharmacology·Praveena BaireddyCarey Pope
Jun 2, 2001·Ecotoxicology and Environmental Safety·S L BeauvaisE E Little
Sep 8, 2006·Toxicology·Anuradha NallapaneniCarey Pope

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