Protein kinase Cα targeting is regulated by temporal and spatial changes in intracellular free calcium concentration [Ca 2+ ] i

2000 ◽  
Vol 14 (11) ◽  
pp. 1653-1663 ◽  
Author(s):  
Christian Maasch ◽  
Stefan Wagner ◽  
Carsten Lindschau ◽  
Gabi Alexander ◽  
Klaus Buchner ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Calcium Concentration ◽  
Intracellular Free Calcium ◽  
Free Calcium ◽  
Spatial Changes ◽  
Protein Kinase Cα ◽  
Intracellular Free Calcium Concentration ◽  
Free Calcium Concentration ◽  
Temporal And Spatial

Role of Protein Kinase C in the Anti-Aggregatory Effects of Endothelin-1 on Human Platelets

1995 ◽  
Vol 88 (3) ◽  
pp. 277-283 ◽  
Author(s):  
R. M. Touyz ◽  
E. L. Schiffrin
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Calcium Concentration ◽  
Human Platelets ◽  
Intracellular Free Calcium ◽  
Free Calcium ◽  
Endothelin 1 ◽  
Kinase C ◽  
Intracellular Free Calcium Concentration ◽  
Free Calcium Concentration

1. Endothelin-1 has anti-aggregatory properties, but the mechanism underlying this inhibitory action is unknown. This in vitro study investigates effects of endothelin-1 on thrombin-stimulated aggregation and intracellular free calcium concentration in human platelets and assesses the role of protein kinase C in the interactions between endothelin-1 and thrombin. Aggregation was measured turbidometrically and the intracellular free calcium concentration was determined with the fluorescent indicator fura 2-acetoxymethyl ester. 2. Endothelin-1 at concentrations from 10−11 to 10−6 mol/l had no effect on platelet aggregation or intracellular free calcium concentration but inhibited in a dose-dependent manner aggregation induced by 0.05 unit/ml thrombin (pD2 for inhibition by endothelin = 8.1 ± 0.12). 3. Endothelin-1 at 10−9 mol/l significantly decreased (P<0.01) thrombin-stimulated aggregation from 81.4 ± 1.5% (in the absence of endothelin-1) to 53.5 ± 1.1% (in the presence of endothelin) and thrombin-stimulated intracellular free calcium concentration from 179 ± 1.7 nmol/l to 140 ± 1.8 nmol/l. 4. Preincubation of platelets with 10−7 mol/l staurosporine (protein kinase C inhibitor), calphostin C (highly selective protein kinase C inhibitor) or 5-(N,N-hexamethylene) amiloride (highly selective Na+-H+ exchange blocker) significantly inhibited (P < 0.01) thrombin-stimulated platelet responses and suppressed the inhibitory effect of endothelin-1 on thrombin-induced aggregation and intracellular free calcium concentration. 5. In conclusion, endothelin-1 decreases the aggregatory response of human platelets to thrombin by mechanisms that probably involve protein kinase C and Na+-H+ linked pathways.

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