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Protein kinase C plays a key role in the cross-talk between intracellular signalings via prostanoid receptors in a megakaryoblastic cell line, MEG-01s

Authors
  • Tsuyoshi Watanabe,
  • Shinji Sunaga,
  • Masako Togo,
  • Hiroaki Satoh,
  • Masaaki Higashihara,
  • Yoshiaki Hashimoto,
  • Kiyoshi Kurokawa,
Type
Published Article
Journal
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism
Publisher
Elsevier
Publication Date
Jan 01, 1996
Accepted Date
Jul 31, 1996
Volume
1304
Issue
2
Pages
161–169
Identifiers
DOI: 10.1016/S0005-2760(96)00111-7
Source
Elsevier
Keywords
License
Unknown

Abstract

In a previous study, we characterized prostanoid and thrombin receptors expressed on a megakaryoblastic cell line, MEG-01s (Blood 78, 2328–2336, 1991). In this study, we examines the mechanism of cross-talk between intracellular Ca 2+ ([Ca 2+] i) and cAMP signalings through prostanoid and thrombin receptors. Addition of a thromboxane (TX)A 2 mimetic (U46619 or STA 2) or thrombin stimulated the formation of inositol phosphates and dose-dependently augmented a prostaglandin (PG)I 2 mimetic (iloprost)- or forskolin-induced cAMP formation. 12- O-tetradecanoylphorbol-13-acetate (TPA) and ionomycin, to lesser extent, also augmented iloprost-induced cAMP formation. The enhancing effect of U46619 or TPA on cAMP formation was inhibited by prolonged pretreatment of the cells with TPA (2.5 μM, 24h), but not with calmodulin-antagonists; W-7, W-5, or KN-62. The elevation of [Ca 2+] i induced by thrombin, STA 2 or PGE 2 was significantly suppressed by pretreatment of the cells with TPA (100 nM) as well as cAMP mimetics such as dibutyryl cAMP (5 mM), forskolin (5 μM) and iloprost (1 μM). These results suggest the key role of PKC on the cross-talk between [Ca 2+] i and cAMP signalings through prostanoid and thrombin receptors; PKC, which is activated with TXA 2, or thrombin, concomitantly suppress further [Ca 2+] i elevation and enhances the PGI 2 receptor-mediated cAMP formation, which, in turn, suppress [Ca 2+] i elevation.

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