DOSE-DEPENDENT INHIBITION OF PHOSPHOLIPASE A(2) BY PARAOXON IN-VITRO - PRELIMINARY-RESULTS

To establish the dose dependency of phospholipase A(2) (PLA(2)) inhibi tion by the organophosphorus compound (OPC) paraoxon (POX), human plat elet membranes were incubated after Ca2+ removal (to inactivate the PL A(2)) with 0.3, 1 and 3 mu g ml(-1) POX for 5, 30 and 60 min each, The PLA(2) activity (pmol mg(-1) protein min(-1)) was measured after subs equent enzyme reactivation, The PLA(2) activity in native platelets wa s considered to be 100%; all other measured values are expressed as a percentage thereof, Data were analysed with the Mann-Whitney Wilcoxon rank order test and ANOVA, Statistical significance was assumed for P less than or equal to 0.01, Paraoxon inhibited in a dose-dependent man ner the PLA(2) activity, Different incubation times of the inactive PL A(2) with POX did not have any additional effect on the activity reduc tion after activation, At the tested POX concentrations the PLA(2) act ivity was 42 +/- 5.4%, 29 +/- 3.4% and 15 +/- 6.6%, respectively, The corresponding butyrylcholine esterase (BChE) activities were much less than 1% of the baseline activity, Phospholipase A(2) is less sensitiv e to POX inhibition than BChE and, at clinically achievable POX concen trations, shows a clear dose dependency, Further work is needed to elu cidate the exact mechanism and time dependency of the phenomenon. (C) 1997 by John Wiley & Sons, Ltd.