Inhibition of thrombin-induced Ca²⁺ influx in platelets by R59949, an inhibitor of diacylglycerol kinase

The Journal of Pharmacy and Pharmacology
Mikio MarumoIchiro Wakabayashi

Abstract

The aim of this study was to determine whether diacylglycerol kinase (DGK) is involved in transplasmalemmal Ca²⁺ influx of platelets. Effects of R59949, an inhibitor of diacylglycerol kinase, on intracellular Ca²⁺ concentration ([Ca²⁺](i) ) and mRNA expression of DGK isozymes were investigated using washed human platelet suspensions. Thrombin-induced increase in [Ca²⁺](i) was significantly inhibited by pretreatment of platelets with R59949, while thapsigargin-induced increase in [Ca²⁺](i) was comparable in platelets with and without R59949 pretreatment. Thapsigargin-induced increase in [Ca²⁺](i) was markedly attenuated in the presence of SKF-96365. In the presence of SKF-96365, thrombin-induced increase in [Ca²⁺](i) was significantly attenuated, and additional treatment with R59949 caused a further decrease in [Ca²⁺](i) . Pretreatment of platelets with 1-butanol significantly attenuated thrombin-induced increase in [Ca²⁺](i) , while thrombin-induced increase in [Ca²⁺](i) was augmented in the presence of propranolol. mRNA expression of DGK-α and DGK-γ, which are known to be inhibited by R59949, in platelets was confirmed by RT-PCR analysis. R59949 inhibited a store-depletion-insensitive component of transplasmalemmal Ca²⁺ entry ...Continue Reading

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Citations

Sep 24, 2020·International Journal of Molecular Sciences·Jae Ang SimDongki Yang
Apr 11, 2019·Blood Advances·Alyssa J MoroiPeter J Newman
Oct 1, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Benjamin Purow

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