THE MODE OF INHIBITION OF HUMAN ERYTHROCYTE MEMBRANE-BOUND ACETYLCHOLINESTERASE BY CISPLATIN IN-VITRO

The effect of the well known anticancer drug ''cisplatin'' on the huma n erythrocyte membrane-bound acetylcholinesterase (AChE) has been inve stigated. It was found that cisplatin has inhibitory activity against AChE. Cisplatin (0.5-7.0 mM) inhibited AChE activity (27-82%) in a con centration dependent manner. The nature of the inhibition of AChE by c isplatin was complex and involved a partial reversible stage followed by a slow acting irreversible step. The inhibition was independent of a preincubation period up to 90 min while becoming dependent after thi s period. By diluting the preincubated AChE-cisplatin mixture for diff erent times (0-24 h), the inhibition was partially reversed but again increased progressively with incubation time, ultimately reaching comp lete inhibition. The effect of increasing substrate concentration had the same behaviour as the dilution effect.