A study of human erythrocyte acetylcholinesterase inhibition by chlorpromazine

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

Research output: Contribution to journalArticle

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

Fingerprint

Chlorpromazine
Acetylcholinesterase
Erythrocytes
Phosphoinositide Phospholipase C
Octoxynol
Membranes
Molecular interactions
Bacilli
Enzymes
Membrane Lipids
Bacillus thuringiensis
Pharmaceutical Preparations
Erythrocyte Membrane
Kinetics

ASJC Scopus subject areas

  • Biochemistry

Cite this

Spinedi, A., Pacini, L., Limatola, C., Luly, P., & Farias, R. N. (1991). A study of human erythrocyte acetylcholinesterase inhibition by chlorpromazine. Biochemical Journal, 278(2), 461-463.

A study of human erythrocyte acetylcholinesterase inhibition by chlorpromazine. / Spinedi, A.; Pacini, L.; Limatola, C.; Luly, P.; Farias, R. N.

In: Biochemical Journal, Vol. 278, No. 2, 1991, p. 461-463.

Research output: Contribution to journalArticle

Spinedi, A, Pacini, L, Limatola, C, Luly, P & Farias, RN 1991, 'A study of human erythrocyte acetylcholinesterase inhibition by chlorpromazine', Biochemical Journal, vol. 278, no. 2, pp. 461-463.
Spinedi, A. ; Pacini, L. ; Limatola, C. ; Luly, P. ; Farias, R. N. / A study of human erythrocyte acetylcholinesterase inhibition by chlorpromazine. In: Biochemical Journal. 1991 ; Vol. 278, No. 2. pp. 461-463.
@article{677ac0fbdb50415f9637e4a5d6876a70,
title = "A study of human erythrocyte acetylcholinesterase inhibition by chlorpromazine",
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.",
author = "A. Spinedi and L. Pacini and C. Limatola and P. Luly and Farias, {R. N.}",
year = "1991",
language = "English",
volume = "278",
pages = "461--463",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "2",

}

TY - JOUR

T1 - A study of human erythrocyte acetylcholinesterase inhibition by chlorpromazine

AU - Spinedi, A.

AU - Pacini, L.

AU - Limatola, C.

AU - Luly, P.

AU - Farias, R. N.

PY - 1991

Y1 - 1991

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0025784956&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025784956&partnerID=8YFLogxK

M3 - Article

C2 - 1654884

AN - SCOPUS:0025784956

VL - 278

SP - 461

EP - 463

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 2

ER -