A study of human erythrocyte acetylcholinesterase inhibition by chlorpromazine

A. Spinedi, L. Pacini, C. Limatola, P. Luly, R. N. Farias

Research output: Contribution to journalArticlepeer-review

Abstract

Membrane-bound acetylcholinesterase (AChE) from the human erythrocyte is inhibited by chloropromazine (CPZ) in a concentration range within which this amphiphilic drug has been demonstrated to interact with erythrocyte membranes, causing a large spectrum of physical and structural effects; membrane solubilization with 0.5% Triton X-100 results in a complete loss of CPZ inhibitory potency. Although these observations might suggest a role for membrane lipid environment in mediating human erythrocyte AChE inhibition, we observed that CPZ retains its full inhibitory effect on the fraction of enzyme (5-6% of total) that is solubilized from erythrocytes upon treatment with phosphatidylinositol- specific phospholipase C (Pl-PLC) from Bacillus thuringiensis; furthermore, Triton X-100 is able to reverse the CPZ effect also in the case of Pl-PLC-solubilized enzyme. These results demonstrate unequivocally that CPZ inhibits human erythrocyte AChE through direct molecular interaction. The inhibition kinetics displayed by CPZ on human erythrocyte AChE are dependent on drug concentration: evidence is provided that this phenomenon may be related to formation of CPZ micellar aggregates.

Original languageEnglish
Pages (from-to)461-463
Number of pages3
JournalBiochemical Journal
Volume278
Issue number2
Publication statusPublished - 1991

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'A study of human erythrocyte acetylcholinesterase inhibition by chlorpromazine'. Together they form a unique fingerprint.

Cite this