RAT-BRAIN ACETYLCHOLINESTERASE ACTIVITY - DEVELOPMENTAL PROFILE AND MATURATIONAL SENSITIVITY TO CARBAMATE AND ORGANOPHOSPHORUS INHIBITORS

A growing body of evidence indicates that young animals exhibit an inc reased susceptibility to the lethal effects of cholinesterase (ChE)-in hibiting insecticides. Our laboratory is engaged in defining factors w hich may explain this age-related sensitivity. This report includes re sults from experiments designed to compare the developmental profiles, kinetic parameters and intrinsic (i.e, in vitro) sensitivity of devel oping male rat brain acetylcholinesterase (AChE) activity to carbamate and organophosphorus anticholinesterases. Total ChE activity in whole brain for each age was composed of about 90% AChE and 10% butyrylchol inesterase (BuChE) activity for the six ages examined. Brain AChE acti vity showed an age-related increase in V-max until postnatal day 17 wi th no change in K-m (average of all six ages similar to 72 mu M). Opti mal substrate (acetylthiocholine) concentration for each age was 1 mM, and there was substrate inhibition (approximate to 10%) at 2.5 mM. IC (50)s (the concentration of compound that inhibits 50% of the AChE act ivity in 30 min at 26 degrees C) defined concomitantly for postnatal d ay 4 and adult brain AChE using either aldicarb, carbaryl, chlorpyrifo s-oxon or malaoxon were virtually identical at both ages with average IC50 values being: aldicarb = 2.4 mu M, carbaryl = 1.7 mu M, chlorpyri fos-oxon = 4.9 nM and malaoxon = 140 nM. In summary, AChE in young and adult brain differs mostly in specific activity while the K(m)s, subs trate profiles, and in vitro sensitivity to selected anticholinesteras e insecticides are not different. Therefore, these data support the hy pothesis that the greater sensitivity of the young animals to antichol inesterase pesticides is not due to the greater sensitivity of the tar get molecule AChE to these inhibitors. (C) 1998 Elsevier Science Irela nd Ltd. All rights reserved.