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

In this study dosing regimens were designed such that cholinesterase inhibi tion following exposure to chlorpyrifos was produced in one treatment group . but was absent in the other. The higher dosing regimen inhibited plasma a nd brain cholinesterase activities by 51 and 70%, respectively, and resulte d in decreased [H-3]cis-methyldioxolane ([H-3]CD) binding, which was attrib utable to a decrease in B-max. No concomitant loss Of [H-3]quinuclidinyl be nzilate ([H-3]QNB) binding sites was observed., indicating that the M, musc arinic receptor subtype to which [H-3]CD binds is particularly susceptible to alterations induced by chlorpyrifos treatment. As the M-2 receptor subty pe is surmised to be the muscarinic autoreceptor, decreases in this recepto r may exacerbate poisoning by organophosphorus agents as a result of decrea sed ability to terminate synaptic acetylcholine release. The ability of car bachol to inhibit striatal adenylate cyclase, which is an effector molecule associated with the M-2 receptor., was unaltered in chlorpyrifos-treated r ats. Decreases in M-2 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 a s a result of sub-chronic chlorpyrifos exposure. Such alterations may contr ibute to neurological impairments that develop following chronic organophos phorus exposure.