INTERSPECIES DIFFERENCES IN ENZYMES REACTING WITH ORGANOPHOSPHATES AND THEIR INHIBITION BY PARAOXON IN-VITRO

1 Inhibition of cholinesterases (ChE) and carboxylesterases (CaE) by p araoxon (Px) was studied in vivo in the serum, liver, lung and muscle of mouse, guineapig, rabbit and man (serum only). Moreover, the role o f Px hydrolyzing enzyme (Pxase) in the detoxification of Px was studie d by inhibiting its activity with EDTA. 2 The ChE and CaE activities a s well as their sensitivity to Px varied in different tissues and spec ies. The ChEs were more sensitive than CaEs to Px except in the liver. The CaE activity in human and rabbit sera was low and resistant to Px , indicating that it may have a minor importance for the binding of Px . 3 The Px-inhibited ChEs were spontaneously reactivated in the mouse and rabbit sera during 24 h. In mouse, also the CaE activity was recov ered. The presence of EDTA in the incubation medium prevented this rea ctivation indicating that Pxase takes part in the reactivation process . 4 In rabbit, the serum Pxase activity was very high suggesting a goo d Px detoxifying capacity of the rabbit serum. 5 The results show that amounts and sensitivities of esterases to OPs in rodents may markedly differ from that in man. Possible species-related differences in the affinity of ChEs and CaEs for OPs and the OP hydrolyzing activity shou ld be taken into the consideration, when animal data are extrapolated to man.