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 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.
Strunecká
A
A
Department of General Physiology, Faculty of Natural Sciences, Charles University, Prague.
Rípová
D
D
Folk
P
P
D000255:Adenosine Triphosphate / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010712:Phosphatidic Acids / Q000097:blood; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000097:blood*; D010766:Phosphorylation; D013917:Thrombin / Q000494:pharmacology
D001798:Blood Proteins; D010712:Phosphatidic Acids; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C037178:phosphatidylinositol 4-phosphate; D000255:Adenosine Triphosphate; D013917:Thrombin; D002746:Chlorpromazine