The mode of inhibition of human erythrocyte membrane-bound acetylcholinesterase by cisplatin in vitro

J Enzyme Inhib. 1995;8(4):281-9. doi: 10.3109/14756369509020135.

Abstract

The effect of the well known anticancer drug "cisplatin" on the human erythrocyte membrane-bound acetylcholinesterase (AChE) has been investigated. It was found that cisplatin has inhibitory activity against AChE. Cisplatin (0.5-7.0 mM) inhibited AChE activity (27-82%) in a concentration dependent manner. The nature of the inhibition of AChE by cisplatin 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 this period. By diluting the preincubated AChE-cisplatin mixture for different times (0-24 h), the inhibition was partially reversed but again increased progressively with incubation time, ultimately reaching complete inhibition. The effect of increasing substrate concentration had the same behaviour as the dilution effect.

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Acetylthiocholine / metabolism
  • Cholinesterase Inhibitors*
  • Cisplatin / pharmacology*
  • Dose-Response Relationship, Drug
  • Erythrocyte Membrane / enzymology
  • Humans
  • Hydrolysis
  • Male
  • Time Factors

Substances

  • Cholinesterase Inhibitors
  • Acetylthiocholine
  • Acetylcholinesterase
  • Cisplatin