Effect of chlorpromazine on inositol-lipid signalling system in human thrombocytes

The effect of 0.5 mmol/l chlorpromazine (CPZ) on phospholipid metabolism, ATP content, and protein phosphorylation was studied in isolated human platelets. After 30 min incubation CPZ reduced the ATP content of the cells to 17% of the control. At the same time, the radioactivity in 32P prelabelled i...

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Bibliographic Details
Published inPhysiologia Bohemoslovaca Vol. 36; no. 6; p. 495
Main Authors Strunecká, A, Rípová, D, Folk, P
Format Journal Article
LanguageEnglish
Published Czech Republic 1987
Subjects
Adenosine Triphosphate - blood
Blood Platelets - drug effects
Blood Platelets - metabolism
Blood Proteins - metabolism
Chlorpromazine - pharmacology
Humans
In Vitro Techniques
Phosphatidic Acids - blood
Phosphatidylinositol 4,5-Diphosphate
Phosphatidylinositol Phosphates
Phosphatidylinositols - blood
Phosphorylation
Thrombin - pharmacology
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Summary:The effect of 0.5 mmol/l chlorpromazine (CPZ) on phospholipid metabolism, ATP content, and protein phosphorylation was studied in isolated human platelets. After 30 min incubation CPZ reduced the ATP content of the cells to 17% of the control. At the same time, the radioactivity in 32P prelabelled inositol lipids--phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol (PI), and phosphatidic acid (PA) decreased to 30, 51, and 61% of the controls, respectively, whereas an increase up to 188% of the control was observed in phosphatidylinositol 4-phosphate (PIP). A massive dephosphorylation of proteins was found. Thrombin, added to 32P prelabelled platelets for 90 s, increased the levels of radioactivity in phosphoinositides and PA. When added to CPZ--pretreated 32P prelabelled platelets, thrombin decreased the radio-activity in PIP2, PIP, and PA to 4, 86, and 10% of the control, respectively. We assume that the pharmacological effect of CPZ might be connected with the decreased ATP content, decreased PIP2 pool and with the impairment of protein phosphorylation.
ISSN:0369-9463