Membrane-bound acetylcholinesterase (AChE) from the human erythrocyte is inhibited by chlorpromazine (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 (PI-PLC) from Bacillus thuringiensis; furthermore, Triton X-100 is able to reverse the CPZ effect also in the case of PI-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.

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, ANGELO;LULY, PAOLO;
1991-01-01

Abstract

Membrane-bound acetylcholinesterase (AChE) from the human erythrocyte is inhibited by chlorpromazine (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 (PI-PLC) from Bacillus thuringiensis; furthermore, Triton X-100 is able to reverse the CPZ effect also in the case of PI-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.
1991
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/09 - FISIOLOGIA
English
Con Impact Factor ISI
acetylcholinesterase; chlorpromazine; membrane lipid; phospholipase c; triton x 100; article; drug concentration; erythrocyte; erythrocyte membrane; molecular interaction; priority journal; solubilization; Acetylcholinesterase; Bacillus thuringiensis; Chlorpromazine; Cholinesterase Inhibitors; Detergents; Erythrocyte Membrane; Fluorescence Polarization; Human; Kinetics; Octoxynol; Phosphoric Diester Hydrolases; Polyethylene Glycols; Support, Non-U.S. Gov't; Bacillus thuringiensis
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.
Spinedi, A; Pacini, L; Limatola, C; Luly, P; Farias, Rn
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/54830
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