In:
Journal of Pharmacy and Pharmacology, Oxford University Press (OUP), Vol. 64, No. 6 ( 2012-05-10), p. 855-861
Kurzfassung:
The aim of this study was to determine whether diacylglycerol kinase (DGK) is involved in transplasmalemmal Ca2+ influx of platelets. Methods 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. Key findings 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. Conclusions R59949 inhibited a store-depletion-insensitive component of transplasmalemmal Ca2+ entry induced by thrombin, while store-operated Ca2+ entry was not affected by R59949. The results of this study suggest that phosphatidic acid is involved in thrombin-induced Ca2+ influx of platelets.
Materialart:
Online-Ressource
ISSN:
2042-7158
,
0022-3573
DOI:
10.1111/j.2042-7158.2012.01485.x
Sprache:
Englisch
Verlag:
Oxford University Press (OUP)
Publikationsdatum:
2012
ZDB Id:
2041988-0
ZDB Id:
2050532-2
SSG:
15,3
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