Huff_2001_Arch.Toxicol_75_480

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