Chlorpromazine Inhibits Vesiculation, Alters Phosphoinositide Turnover and Changes Deformability of ATP-Depleted RBCs

To delineate further the underlying mechanism by which amphiphilic drugs can modulate vesicle release from human RBCs, we studied the effect of chlorpromazine on erythrocyte vesiculation induced by ATP depletion. This was correlated with turnover of the phosphoinositides as well as RBC deformability...

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Bibliographic Details
Published in:Blood 1989-05, Vol.73 (6), p.1699-1704
Main Authors: Bütikofer, Peter, Lin, Zeng Wen, Kuypers, Frans A., Scott, Mark D., Xu, Caimin, Wagner, Gail M., Chiu, Daniel T.-Y., Lubin, Bertram
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - blood
Biological and medical sciences
Chlorpromazine - pharmacology
Erythrocyte Deformability - drug effects
Erythrocyte Membrane - drug effects
Erythrocytes - drug effects
Erythrocytes - physiology
Humans
In Vitro Techniques
Medical sciences
Membrane Lipids - blood
Membrane Proteins - blood
Neuropharmacology
Pharmacology. Drug treatments
Phosphatidylinositols - blood
Psycholeptics: tranquillizer, neuroleptic
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Time Factors
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Summary:To delineate further the underlying mechanism by which amphiphilic drugs can modulate vesicle release from human RBCs, we studied the effect of chlorpromazine on erythrocyte vesiculation induced by ATP depletion. This was correlated with turnover of the phosphoinositides as well as RBC deformability during the process since phosphoinositide metabolism may be involved in shape regulation of RBCs. Echinocytic shape transformation and subsequent vesiculation of RBCs, which commonly occur during ATP depletion, were inhibited by chlorpromazine. Furthermore, with a newly developed two-dimensional thin-layer chromatography separation of RBC membrane phospholipids, we showed that chlorpromazine significantly decreased the dephosphorylation of phosphatidylinositol-4,5-bisphosphate (PIP2) in both ATP-depleted RBCs as well as in cells with partly maintained ATP levels. Concomitantly, there was a smaller increase in the relative amount of phosphatidylinositol. In addition, chlorpromazine also inhibited the decrease in RBC deformability as well as the shift of osmotic fragility that occurs during ATP depletion of erythrocytes.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V73.6.1699.1699