Physiological Significance of Thromboxane A_2 Receptor Dimerization

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The thromboxane A<sub>2</sub> receptor (TP), one of the G protein-coupled receptors (GPCRs), consists of two splicing variants, TPα and TPβ, which differ in their C-terminal regions. In the present study, we investigated whether TPα and TPβ formed homo- or hetero-dimers and whether the dimerization changed the function of TP. The immunofluorescent analysis using human embryonic kidney (HEK) 293 cells expressing either FLAG-tagged TPα or TPβ showed that TPα is mainly distributed on plasma membranes and TPβ existed on plasma membranes and within the cells. Co-immunoprecipitation analysis using HEK293 cells expressing both TPα and TPβ showed that TPα and TPβ formed homo- and hetero-dimers. U46619, a TP agonist, caused phosphoinositide hydrolysis and elevation of [Ca<sup>2+</sup>]<sub>i</sub> in a concentration-dependent manner in Chinese hamster ovary (CHO) cells expressing TPα or TPβ. The responses were observed to a greater extent in the cells expressing TPα than TPβ. In the cells expressing both TPα and TPβ, U46619-induced responses were observed to a lesser extent than in the cells expressing TPα alone. Furthermore, [<sup>3</sup>H]SQ29548 binding showed that the level of the cell surface expression of TP was the following order: the cells expressing TPα > TPα and TPβ > TPβ. These results indicate that TPα and TPβ formed homo- and hetero-dimers, and TP-mediated signaling may be regulated by the hetero-dimer.<br>

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  • Journal of pharmacological sciences  

    Journal of pharmacological sciences 100(4), 263-270, 2006-04-20 

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10018239855
  • NII書誌ID(NCID)
    AA11806667
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13478613
  • NDL 記事登録ID
    7884910
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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