Muscarinic cholinergic receptor regulation and acetylcholinesterase inhibition in response to insecticide exposure during development.
Neonatal rats were exposed to parathion, an acetylcholinesterase inhibiting organophosphorus pesticide, during a rapid phase of cholinergic receptor development. Rats were given subcutaneous injections of 1.5 mg/kg/day from postnatal days 8-20. The immediate effects of subchronic developmental exposure were assessed in 21-day-old animals and more persistent effects assessed in 36-day-old animals. There was a 61% inhibition of acetylcholinesterase and a 27% decrease of muscarinic receptor density in 21-day-old treated rats. The reduction in receptor density was dose-dependent and a significant correlation was found between the level of acetylcholinesterase inhibition produced by parathion and the reduction in receptor density. It was estimated that a minimum of at least 15% prolonged inhibition of forebrain acetylcholinesterase by parathion was necessary to reduce receptor density. Regional analyses of receptor autoradiograms of 21-day-old animals indicated muscarinic receptors in the cortex and hippocampus were preferentially lost. The anterior thalamus was notable in having a high density of cholinergic receptors which were unaffected by parathion treatment. No changes were found in the affinity of [3H]QNB for the receptor or in the binding of the agonist, acetylcholine, n competition binding studies. AChE activity and muscarinic receptor density returned to normal after a 16 day recovery period. Parathion treated animals were growth inhibited but, growth retardation induced by undernutrition did not alter receptor density or affinity of QNB for muscarinic receptors. Thus, the transient decrease in receptor density in parathion exposed animals was similar to the response previously observed in adults and was not secondary to growth retardation or undernutrition. Receptor densities and acetylcholinesterase levels were regulated back to normal values after a 16 day recovery period in spite of the perturbation of cholinergic function during cholinergic synapse and receptor development.
Dvergsten
C
C
Department of Neurology, University of North Carolina, Chapel Hill 27599.
Meeker
R B
RB
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004334:Drug Administration Schedule; D007306:Insecticides / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D010278:Parathion / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D011976:Receptors, Muscarinic; D010278:Parathion; D000110:Acetylcholinesterase