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 language | English |
|---|---|
| Pages (from-to) | 461-463 |
| Number of pages | 3 |
| Journal | Biochemical Journal |
| Volume | 278 |
| Issue number | 2 |
| Publication status | Published - 1991 |
Fingerprint
ASJC Scopus subject areas
- Biochemistry
Cite this
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 journal › Article
}
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 -