心筋障害の調節因子とアデノシン産生  [in Japanese] Adenosine production and its role in protection against ischemic and reperfusion injury of the myocardium  [in Japanese]

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Abstract

冠循環は,その重要さゆえに心筋虚血などの代謝異常運動,外的ストレス,に対して迅速に対応できる循環制御メカニズムが備わっている.循環系の調節因子はきわめて複雑であるが,神経,心臓,内皮細胞および血球成分はそれぞれから遊出されるケミカルメディエーターにより冠微小循環を個別に調節することが知られている.心臓はエネルギー消費の最も大きい臓器で,容易に虚血に陥る.虚血-再灌流障害による代謝変動と,これにかかわるフリーラジカルが生体内の生理病理現象に広く関わっている.ATPの分解産物であるアデノシンは神経,心筋,内皮細胞および白血球成分のいずれからも産生され,かつどの細胞にも受容体が存在するため冠微小循環調節の各因子のモジュレーターとして冠循環を調節している.アデノシンは虚血や低酸素下で心筋から大量に産生され,冠血流量増大,心筋代謝改善,不整脈に作用する.<br>

Adenosine exerts cardioprotective effects on the ischemic myocardium. A flexibly mounted microdialysis apparatus was used to measure the concentration of interstitial adenosine and to assess the activity of ecto-5'-nucleotidase (a key enzyme responsible for adenosine production) in in vivo rat hearts. The level of adenosine during adenosine 5'-adenosine monophosphate (AMP) perfusion serves as an index of the activity of ecto-5'-nucleotidase in the tissue. Endogenous norepinephrine (NE) activates α<sub>1</sub>-adrenoceptors to lead to the activation of protein kinase C (PKC), which, in turn, activates ecto-5'-nucleotidase via phosphorylation, thereby enhancing the production of interstitial adenosine. Histamine-induced release of NE activates PKC, which increases ecto-5'-nucleotidase activity and augments release of adenosine. Nicorandil, a hybrid of an ATP sensitive K<sup>+</sup> (K<sub>ATP</sub>) channel opener and nitrate, increases the level of interstitial adenosine via cGMP-mediated activation of ecto-5'-nucleotidase. Opening of cardiac K<sub>ATP</sub> channels may cause hydroxyl radical (·OH) generation. Nitric oxide (NO) facilitates the production of interstitial adenosine, via activation of ecto-5'-nucleotidase. However, singlet oxygen (<sup>1</sup>O<sub>2</sub>) is a very powerful oxidant that causes inactivation of ecto-5'-nucleotidase to result in a decrease in the concentration of adenosine in rat heart. Adenosine plays an important role as a modulator of ischemic reperfusion injury. The production and action of adenosine are intimately linked to the release of NE.<br>

Journal

  • Folia Pharmacologica Japonica

    Folia Pharmacologica Japonica 119(5), 273-279, 2002-05-01

    The Japanese Pharmacological Society

References:  37

Codes

  • NII Article ID (NAID)
    10008991991
  • NII NACSIS-CAT ID (NCID)
    AN00198335
  • Text Lang
    JPN
  • Article Type
    REV
  • ISSN
    00155691
  • NDL Article ID
    6148759
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z19-247
  • Data Source
    CJP  NDL  J-STAGE 
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