Carboxylesterases in guinea pig. A comparison of the different isoenzymes with regard to inhibition by organophosphorus compounds in vivo and in vitro.
The different isoenzymes of carboxylesterase (CarbE) from guinea pig liver, lung and plasma were separated by gel filtration and chromatofocusing. The isoenzymes were characterized by inhibition with several different organophosphorus compounds. The bimolecular rate constants showed the same tendency of decreased inhibition for all of the isoenzymes in the order; paraoxon greater than soman greater than diisopropylphosphofluoridate (DFP) greater than bis(p-nitrophenyl)phosphate. With two exceptions the inhibition constants for the different isoenzymes differed little. Subcutaneous and intraperitoneal administration of DFP and paraoxon rapidly inhibited the CarbE activity in guinea pig plasma. Much higher doses were necessary to obtain a marked inhibition in lung and liver. About 25% of CarbE activity in lung was resistant to paraoxon and DFP inhibition. Gel filtration of lung homogenate after treatment with the organophosphorus compounds showed that the CarbE activity of the medium molecular mass fractions was inhibited only weakly. This could be due to reduced accessibility to some of the lung CarbE isoenzymes.
Norwegian Defence Research Establishment, Division for Environmental Toxicology, Kjeller.
R
R
Gaustad
H
H
Johnsen
F
F
Fonnum
D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors* / Q000097:blood / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007525:Isoelectric Focusing; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000097:blood / Q000302:isolation & purification; D007531:Isoflurophate / Q000008:administration & dosage / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000633:toxicity*; D010261:Paraoxon / Q000008:administration & dosage / Q000633:toxicity
D007527:Isoenzymes; D009943:Organophosphorus Compounds; D007531:Isoflurophate; D002265:Carboxylic Ester Hydrolases; D010261:Paraoxon