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Kinetic analysis of the in vitro inhibition, aging, and reactivation of brain acetylcholinesterase from rat and channel catfish by paraoxon and chlorpyrifos-oxon.
Toxicol Appl Pharmacol. 1996 Aug; 139(2):365-73.TA

Abstract

In rats, the phosphorothionate insecticide parathion exhibits greater toxicity than chlorpyrifos, while in catfish the toxicities are reversed. The in vitro inhibition of brain acetylcholinesterase (AChE) by the active metabolites of the insecticides and the rates at which these inhibitor-enzyme complexes undergo reactivation/ aging were investigated in both species. Rat AChE was more sensitive to inhibition than catfish AChE as demonstrated by greater bimolecular rate constants (ki) in rats than in catfish. In both species, chlorpyrifos-oxon yielded higher ki's than paraoxon. The higher association constant (KA) of chlorpyrifos-oxon than paraoxon in both species and the lack of significant differences in the phosphorylation constants (kp) suggest that association of the inhibitor with AChE is the principal factor in the different potencies between these two inhibitors. In catfish, the ki of chlorpyrifos-oxon was 22-fold greater than that of paraoxon, while in rats it was 9-fold greater, suggesting that target site sensitivity is an important factor in the higher toxicity of chlorpyrifos to catfish but not in the higher toxicity of parathion to rats. No spontaneous reactivation of phosphorylated catfish AChE occurred and there were no differences in the first oder aging constants (ka) between compounds. For phosphorylated rat AChE, there were no differences in the first order reactivation constants (kr) but the ka for chlorpyrifos-oxon was significantly greater than that for paraoxon. This difference suggests that the steric positioning of the diethyl phosphate in the esteratic site is not the same between the two compounds, leading to differences in aging.

Authors+Show Affiliations

Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University 39762, USA.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8806854

Citation

Carr, R L., and J E. Chambers. "Kinetic Analysis of the in Vitro Inhibition, Aging, and Reactivation of Brain Acetylcholinesterase From Rat and Channel Catfish By Paraoxon and Chlorpyrifos-oxon." Toxicology and Applied Pharmacology, vol. 139, no. 2, 1996, pp. 365-73.
Carr RL, Chambers JE. Kinetic analysis of the in vitro inhibition, aging, and reactivation of brain acetylcholinesterase from rat and channel catfish by paraoxon and chlorpyrifos-oxon. Toxicol Appl Pharmacol. 1996;139(2):365-73.
Carr, R. L., & Chambers, J. E. (1996). Kinetic analysis of the in vitro inhibition, aging, and reactivation of brain acetylcholinesterase from rat and channel catfish by paraoxon and chlorpyrifos-oxon. Toxicology and Applied Pharmacology, 139(2), 365-73.
Carr RL, Chambers JE. Kinetic Analysis of the in Vitro Inhibition, Aging, and Reactivation of Brain Acetylcholinesterase From Rat and Channel Catfish By Paraoxon and Chlorpyrifos-oxon. Toxicol Appl Pharmacol. 1996;139(2):365-73. PubMed PMID: 8806854.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kinetic analysis of the in vitro inhibition, aging, and reactivation of brain acetylcholinesterase from rat and channel catfish by paraoxon and chlorpyrifos-oxon. AU - Carr,R L, AU - Chambers,J E, PY - 1996/8/1/pubmed PY - 1996/8/1/medline PY - 1996/8/1/entrez SP - 365 EP - 73 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 139 IS - 2 N2 - In rats, the phosphorothionate insecticide parathion exhibits greater toxicity than chlorpyrifos, while in catfish the toxicities are reversed. The in vitro inhibition of brain acetylcholinesterase (AChE) by the active metabolites of the insecticides and the rates at which these inhibitor-enzyme complexes undergo reactivation/ aging were investigated in both species. Rat AChE was more sensitive to inhibition than catfish AChE as demonstrated by greater bimolecular rate constants (ki) in rats than in catfish. In both species, chlorpyrifos-oxon yielded higher ki's than paraoxon. The higher association constant (KA) of chlorpyrifos-oxon than paraoxon in both species and the lack of significant differences in the phosphorylation constants (kp) suggest that association of the inhibitor with AChE is the principal factor in the different potencies between these two inhibitors. In catfish, the ki of chlorpyrifos-oxon was 22-fold greater than that of paraoxon, while in rats it was 9-fold greater, suggesting that target site sensitivity is an important factor in the higher toxicity of chlorpyrifos to catfish but not in the higher toxicity of parathion to rats. No spontaneous reactivation of phosphorylated catfish AChE occurred and there were no differences in the first oder aging constants (ka) between compounds. For phosphorylated rat AChE, there were no differences in the first order reactivation constants (kr) but the ka for chlorpyrifos-oxon was significantly greater than that for paraoxon. This difference suggests that the steric positioning of the diethyl phosphate in the esteratic site is not the same between the two compounds, leading to differences in aging. SN - 0041-008X UR - https://www.unboundmedicine.com/medline/citation/8806854/Kinetic_analysis_of_the_in_vitro_inhibition_aging_and_reactivation_of_brain_acetylcholinesterase_from_rat_and_channel_catfish_by_paraoxon_and_chlorpyrifos_oxon_ DB - PRIME DP - Unbound Medicine ER -