1998 Fiscal Year Final Research Report Summary
RESEARCH OF THROMBOXANE A_2 RECEPTOR SUBCLASS AND THEIR SIGNAL TRANSDUCTION
| Project/Area Number |
09470497
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
NAKAHATA Norimichi TOHOKU UNIVERSITY,FACULTY OF PAHRMACEUTICAL SCIENCES,DEPARTMENT OF PHARMACEUTICAL MOLECILAR BIOLOGY/ASSOCIATE PROFESSOR, 薬学部, 助教授 (60045804)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Thromboxane A_2 / Thromboxane A_2 receptor / Thromboxane A_2 receptor subclass / Signal transduction / G_q / G_<12> / phosphatidylcholine / Mitogen-activated protein kinase |
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| Research Abstract |
We found for the first time that 1321N1 human astrocytoma cells express thromboxane A_2 (TXA_2) receptor in 1989. The stimulation of TXA_2 receptor resulted in Ca^<2+> -mobilization mediated via pertussis toxin-insensitive, G protein, Gq, phospholipase C-beta (PLC- beta) and inositol 1,4,5-trisphosphate (TP3) accumulation. Analysis of TXA_2 receptor in platelets and vascular smooth muscles revealed that TXA_2 receptor stimulation caused an activation of a signaling pathway other than Gq/PLC-beta/IP_3/Ca^<2+> pathway. The present study was undertaken to clarify the TXA_2-receptor-mediated signaling pathway other than Gq/PLC-beta/IP_3/Ca^<2+> pathway. In human astrocytoma cells, TXA_2 receptor was coupled to a new pertussis toxin-insensitive G protein G_<12>. The stimulation of TXA_2 receptor resulted in activation of mitogen-activated protein kinase (MAPK) mediated via phosphatidylcholine-specific phospholipase C (PC-PLC) and protein kinase C.The human astrocytoma cells also expressed two alternative splicing products of TXA_2 receptor, placental and endothelial types. In the differentiated astrocytoma cells by dibutyryl cyclic AMP, TXA_2 receptor stimulation caused a weak Ca^<2+> mobilization, but a potent activation of MAPK.These results indicate that G_<12>/PC-PLC pathway is a novel-signaling pathway of TXA_2 receptor stimulation.
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