Differential cholinesterase inhibition and muscarinic receptor changes in CD-1 mice made tolerant to malathion.
The lethality of organophosphate (OP) cholinesterase (CHE) inhibitors is thought to result from depression of the respiratory center in the brain stem, constriction of and increased secretion by the airways, and paralysis of the respiratory musculature. While tolerance to the cholinergic toxicity of OPs has been well documented, such studies have not included investigations of the brain stem and extrapulmonary airways. In this report tolerance to the insecticide malathion is demonstrated. At 24 hr after 14 daily doses of malathion (400 mg/kg, ip), CHE activities were 27, 26, and 28% of control in striatum (ST), hippocampus (HI), and cortex (CX), respectively, while brain stem CHE activity was 41% of control. In addition, the numbers of muscarinic receptors (Bmax) decreased 30, 20, and 22% in ST, HI, and CX, respectively. In contrast, there was no change in brain stem Bmax. The lack of parallelism between CHE inhibition and Bmax effects in brain stem as compared to all other tissues tested raises questions as to the mechanism(s) by which the respiratory system adapts during repeated OP exposure.
D000818:Animals; D001933:Brain Stem / Q000201:enzymology; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002800:Cholinesterase Inhibitors; D003342:Corpus Striatum / Q000201:enzymology; D004361:Drug Tolerance; D008099:Liver / Q000201:enzymology; D008294:Malathion / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012137:Respiratory System / Q000187:drug effects; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D011976:Receptors, Muscarinic; D006899:Mixed Function Oxygenases; D002265:Carboxylic Ester Hydrolases; D008294:Malathion