title: Effects of chronic dermal exposure to nonlethal doses of methyl parathion on brain regional acetylcholinesterase and muscarinic cholinergic receptors in female rats.
abstract: The in vivo and in vitro effects of methyl parathion, a phosphorothionate insecticide, on cholinergic neurotransmitter systems in the brain of rats were investigated. Three groups of adult female rats received 0, 0.1, or 1.0 mg/kg methyl parathion via dermal exposure for 95 days. Exposure to 0.1 mg/kg methyl parathion produced inhibition of AChE in the caudate-putamen and thalamic nuclei, whereas 1.0 mg/kg resulted in inhibition of AChE in most brain regions. The same doses of methyl parathion had no effect on [(3)H]QNB binding to muscarinic receptors in the brain regions examined. The in vitro study demonstrated that methyl parathion causes preferential inhibition of AChE and [(3)H]QNB binding in specific brain regions. As an inhibitor of AChE, methyl paraoxon was 1,000-fold more potent than was methyl parathion. Similarly, methyl paraoxon showed brain region-specific inhibition of the enzyme. Generally, the brain stem was highly sensitive to organophosphate-induced inhibition of AChE activity and [(3)H]QNB binding. Because central respiratory neurons gather in the brain stem, preferential effects there and in other brain regions may underlie lethal toxicity of methyl parathion and other organophosphates.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
authors.forename: Tangeng
authors.initials: T
authors.lastname: Ma
authors.forename: Robert E
authors.initials: RE
authors.lastname: Kramer
authors.forename: Rodney C
authors.initials: RC
authors.lastname: Baker
authors.forename: Lir-Wan
authors.initials: LW
authors.lastname: Fan
authors.forename: Ing K
authors.initials: IK
authors.lastname: Ho
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000279:Administration, Cutaneous; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology; D001933:Brain Stem / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D066298:In Vitro Techniques; D008743:Methyl Parathion / Q000633:toxicity*; D017072:Neostriatum / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D010261:Paraoxon / Q000031:analogs & derivatives* / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism / Q000493:pharmacokinetics; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013788:Thalamus / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D014316:Tritium
chemical_list: D002800:Cholinesterase Inhibitors; D011976:Receptors, Muscarinic; D014316:Tritium; D008743:Methyl Parathion; D011813:Quinuclidinyl Benzilate; D000110:Acetylcholinesterase; D010261:Paraoxon; C008480:methylparaoxon