Affinity for [^3H]Iloprost Binding Sites and cAMP Synthesis Activityof a 3-Oxa-methano Prostaglandin I_1Analog, SM-10906,in Human Platelets and Endothelial Cells

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SM-10902 ((+)-methyl [2-[(2<I>R</I>, 3a<I>S</I>, 4<I>R</I>, 5<I>R</I>, 6a<I>S</I>)-octahydro-5-hydroxy-4-[(<I>E</I>)-(3<I>S</I>, 5<I>S</I>)-3-hydroxy-5-methyl-1-nonenyl]-2-pentalenyl]ethoxy]acetate)and its free acid, SM-10906 are new stable 3-oxamethano prostaglandin (PG)I<SUB>1</SUB> analogs. Their affinities for [<SUP>3</SUP>H]iloprost and [<SUP>3</SUP>H]PGE<SUB>2</SUB> binding sites in human platelets and human umbilical vascular endothelial cells were compared with those of the PGI<SUB>2</SUB> analog iloprost, PGE<SUB>1</SUB> and PGE<SUB>2</SUB> by the radioligand binding assay method. The cyclic AMP (cAMP)synthesis activity of these drugs were also determined in human umbilical vascular endothelial cells. We found that SM-10906 apparently displaced [<SUP>3</SUP>H]iloprost binding to the membrane fractions in those cells since the pK<SUB>i</SUB> values were 6.30 in platelets, 7.52 in vein endothelial cells and 6.31 in the arterial endothelial cells. The pK<SUB>i</SUB> values of SM-10906 for [<SUP>3</SUP>H]PGE<SUB>2</SUB> binding sites were significantly lower than those obtained for [<SUP>3</SUP>H]iloprost binding. SM-10902, which is a prodrug of SM-10906, showed low affinity for [<SUP>3</SUP>H]iloprost binding sites in those cells. SM-10906 also dose-dependently enhanced the cAMP level in the vascular endothelial cells. Thus, these findings indicate that SM-10906 binds to [<SUP>3</SUP>H]iloprost binding sites and exhibits pharmacological functions such as an anti-platelet action and a cytoprotective action in endothelial cells through the elevation of intracellular cAMP contents.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 74(1), 37-43, 1997-05-01

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10008678315
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    4219980
  • 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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