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. 1992 Aug;106(4):966–971. doi: 10.1111/j.1476-5381.1992.tb14443.x

In vitro inhibition by endothelins of thrombin-induced aggregation and Ca2+ mobilization in human platelets.

C Astarie-Dequeker 1, L Iouzalen 1, M David-Dufilho 1, M A Devynck 1
PMCID: PMC1907652  PMID: 1393294

Abstract

1. The in vitro effects of endothelins (ET-1 and ET-3) on human platelets were investigated by measurement of the aggregatory responses of washed platelets to thrombin and by the determination of cytosolic pH (pHi) and free Ca2+ concentration ([Ca2+]i) determined with the fluorescent indicators, BCECF and Fura-2. 2. ET-1 and ET-3 at concentrations ranging from 10(-10) to 5 x 10(-7) M, did not promote platelet aggregation but inhibited in a dose-dependent manner the aggregation induced by 0.05 u ml-1 thrombin (P less than 0.002 and less than 0.001, respectively) with maximal effects reached at 10(-8) M (17 +/- 3 and 15 +/- 2%, n = 11, P = 0.002 for each). 3. Even at 5 x 10(-7) M, ET-1 and ET-3 did not cause a measurable change in basal [Ca2+]i and pHi. When tested in combination with thrombin, 5 x 10(-7) M ET-1 and ET-3 decreased the transient peak of [Ca2+]i by 17 +/- 7 and 28 +/- 7% (n = 7 and 11, P = 0.03 and P = 0.002). No effect on pHi variations was detected. In the virtual absence of external Ca2+, 5 x 10(-7) M ET-3 inhibited the peak of [Ca2+]i by 18 +/- 6% (n = 6, P = 0.02). 4. The anti-aggregating agents, prostacyclin (PGI2, 10(-8)-10(-7) M) and nitroprusside (NP, 10 ng-50 micrograms l-1) also induced a dose-dependent inhibition of the thrombin-induced [Ca2+]i peak (P = 0.001 for each).(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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