ToxSci Advance Access published online on September 26, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg245
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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1 Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University
* To whom correspondence should be addressed. E-mail: chambers{at}cvm.msstate.edu.
Dimethyl phosphorylated cholinesterase (ChE) is known to be more rapidly reactivated spontaneously and have a higher aging rate than diethyl phosphorylated ChE. This may result in differences in toxic signs and tolerance development after treatment of juvenile rats with methyl parathion (MPS), a dimethyl phosphorothionate, than after treatment with chlorpyrifos (CPS), a diethyl phosphorothionate. The effects of repeated MPS exposures on brain ChE activity and surface and total muscarinic acetylcholine receptor (mAChR) density were studied in postnatal rats gavaged daily from postnatal day 1 (PND1) through PND21. Results of this study were compared to our recent report with CPS (Tang et al., 1999, Toxicol. Sci. 51:265-272). Rats received MPS daily starting at 0.3 mg/kg and increasing gradually to 0.6 mg/kg (for the medium dosage groups) and then to 0.9 mg/kg (for the high dosage group). ChE activity was assayed in brain homogenates. Synaptosomal mAChR densities, surface and total, were assayed using 3H-N-methylscopolamine (NMS) and 3H-quinuclidinyl benzilate (QNB), respectively, as ligands. Developmental increases in brain ChE activities and mAChR densities were observed from PND6 through PND22. On PND22, inhibition of ChE activity was observed in the low (26%), medium (42%), and high (55%) dosage groups. Significant inhibition was still present on PND30 (16-24%) and PND40 (12-14%) which were 9 and 19 days after the last treatment, respectively. Densities of 3H-NMS and 3H-QNB binding sites in treated groups were significantly reduced on PND22, 1 day following cessation of treatment, and were significantly increased during the recovery period. After MPS exposure, the initial recovery of phosphorylated ChE was more rapid and the density of 3H-NMS binding sites was less readily reduced than following CPS exposure. The lesser effects on surface mAChR may explain why more severe signs appeared after each treatment with the high dosage of MPS than was observed previously with CPS, indicating little or no tolerance had developed to MPS.
© 2003 Society of Toxicology
Neurotoxicology
The Effects of Repeated Oral Exposures to Methyl Parathion on Rat Brain Cholinesterase and Muscarinic Receptors During Postnatal Development
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