Inhibition of Rat Liver Esterases by Organophosphorus Compounds

Abstract

THE complex family of non-specific carboxylic esterases has been subdivided into different groups, principally on the basis of the results of inhibitor and activator studies¹. One of the most important substances for this purpose is E600 (diethyl-p-nitrophenyl phosphate), which has been used extensively—both biochemically and histochemically—to distinguish between the A and C esterases, which are resistant to organophosphate and unaffected by concentrations of less than 10⁻³ molar E600, and the B esterases, which are sensitive to organophosphate and are completely inhibited by 10⁻⁵ molar E600 (ref. 2). In a histochemical study of indoxylesterases in rat kidney and other tissues, Hess and Pearse³ found that ‘Mipafox’ (N,N′-di-isopropyl phosphorodiamidic fluoride) at a concentration of 10⁻³ moles/l. gave a complete inhibition of B esterases similar to that obtained with 10⁻⁵ molar E600, allowing the subsequent demonstration of A and C esterases. In other tissues⁴, however, it has been found that under histochemical conditions a much higher concentration of E600 than 10⁻⁵ moles/l. is required to produce an inhibition comparable with that of 10⁻³ molar ‘Mipafox’. Increasing concentrations of organophosphate have a progressive inhibiting effect histochemically, which makes it difficult to distinguish clearly between organophosphate-sensitive and organophosphate-resistant enzyme species in terms corresponding to those of biochemical studies.