title: Chlorpromazine inhibits vesiculation, alters phosphoinositide turnover and changes deformability of ATP-depleted RBCs.
abstract: 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 decreased in RBC deformability as well as the shift of osmotic fragility that occurs during ATP depletion of erythrocytes.
authors.affiliation: Children's Hospital Oakland Research Institute, CA 94609.
authors.forename: P
authors.initials: P
authors.lastname: Bütikofer
authors.forename: Z W
authors.initials: ZW
authors.lastname: Lin
authors.forename: F A
authors.initials: FA
authors.lastname: Kuypers
authors.forename: M D
authors.initials: MD
authors.lastname: Scott
authors.forename: C M
authors.initials: CM
authors.lastname: Xu
authors.forename: G M
authors.initials: GM
authors.lastname: Wagner
authors.forename: D T
authors.initials: DT
authors.lastname: Chiu
authors.forename: B
authors.initials: B
authors.lastname: Lubin
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood; D002746:Chlorpromazine / Q000494:pharmacology*; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004910:Erythrocyte Membrane / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008563:Membrane Lipids / Q000097:blood; D008565:Membrane Proteins / Q000097:blood; D010716:Phosphatidylinositols / Q000097:blood; D013997:Time Factors
chemical_list: D008563:Membrane Lipids; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D000255:Adenosine Triphosphate; D002746:Chlorpromazine