Rapid and transient thrombin stimulation of phosphatidylinositol 4,5-bisphosphate synthesis but not of phosphatidylinositol 3,4-bisphosphate independent of phospholipase C activation in platelets.
When platelets are stimulated by thrombin they immediately undergo inositol lipid hydrolysis via phospholipase C activation. However, subsequently an increased production of phosphatidylinositol 4,5-bisphosphate is observed. Phospholipases C were inhibited by lowering the cytoplasmic free calcium concentration by preincubation with Quin-2-tetra(acetoxymethyl) ester. Aggregation and secretion were also totally suppressed. Under these conditions we observed an increased labeling of phosphatidylinositol 4,5-bisphosphate, indicating a stimulation of inositol lipid kinases, independent of lipid hydrolysis by phospholipase C. Conversely the production of phosphatidylinositol 3,4-bisphosphate was totally abolished. These results suggest a different regulation of the kinases/phosphatases responsible for the production of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4-bisphosphate.
INSERM U 326, Phospholipides Membranaires, Signalisation Cellulaire et Lipoprotéines, Hôpital Purpan, Toulouse, France.
C
C
Racaud-Sultan
G
G
Mauco
C
C
Guinebault
M
M
Plantavid
B
B
Payrastre
M
M
Breton
H
H
Chap
D000634:Aminoquinolines / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology*; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007700:Kinetics; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis*; D010716:Phosphatidylinositols / Q000096:biosynthesis*; D010743:Phospholipids / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism*
D000634:Aminoquinolines; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D010743:Phospholipids; C060980:phosphatidylinositol 3,4-diphosphate; D010738:Type C Phospholipases; D013917:Thrombin; C035739:Quin2