Carboxylesterases in Guinea Pig - A Comparison of the Different Isoenzymes withRegard to Inhibition by Organophosphorus Compounds In vivo and In vitro

摘要

The different isoenzymes of carboxylesterase (CarbE) from guinea pig liver, lungand 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 soman diisopropylphosphofluoridate (DEP) 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.