Effects of sub-chronic in vivo chlorpyrifos exposure on muscarinic receptors and adenylate cyclase of rat striatum.


Journal Article

In this study dosing regimens were designed such that cholinesterase inhibition following exposure to chlorpyrifos was produced in one treatment group, but was absent in the other. The higher dosing regimen inhibited plasma and brain cholinesterase activities by 51 and 70%, respectively, and resulted in decreased [3H]cis-methyldioxolane ([3H]CD) binding, which was attributable to a decrease in Bmax. No concomitant loss of [3H]quinuclidinyl benzilate ([3H]QNB) binding sites was observed, indicating that the M2 muscarinic receptor subtype to which [3H]CD binds is particularly susceptible to alterations induced by chlorpyrifos treatment. As the M2 receptor subtype is surmised to be the muscarinic autoreceptor, decreases in this receptor may exacerbate poisoning by organophosphorus agents as a result of decreased ability to terminate synaptic acetylcholine release. The ability of carbachol to inhibit striatal adenylate cyclase, which is an effector molecule associated with the M2 receptor, was unaltered in chlorpyrifos-treated rats. Decreases in M2 receptors occurred with the higher dosing regimen, in the absence of any clinical manifestations. Thus, in the absence of overt clinical signs, perturbations of the muscarinic receptor system did occur as a result of sub-chronic chlorpyrifos exposure. Such alterations may contribute to neurological impairments that develop following chronic organophosphorus exposure.

Full Text

Duke Authors

Cited Authors

  • Huff, RA; Abu-Qare, AW; Abou-Donia, MB

Published Date

  • October 1, 2001

Published In

Volume / Issue

  • 75 / 8

Start / End Page

  • 480 - 486

PubMed ID

  • 11757672

Pubmed Central ID

  • 11757672

International Standard Serial Number (ISSN)

  • 0340-5761

Digital Object Identifier (DOI)

  • 10.1007/s002040100269


  • eng

Conference Location

  • Germany