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[Adenosine production and its role in protection against ischemic and reperfusion injury of the myocardium].

Abstract
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 alpha 1-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+ (KATP) channel opener and nitrate, increases the level of interstitial adenosine via cGMP-mediated activation of ecto-5'-nucleotidase. Opening of cardiac KATP 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 (1O2) 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.
AuthorsToshio Obata
JournalNihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 119 Issue 5 Pg. 273-9 (May 2002) ISSN: 0015-5691 [Print] Japan
PMID12061138 (Publication Type: English Abstract, Journal Article, Review)
Chemical References
  • Potassium Channels
  • Hydroxyl Radical
  • 5'-Nucleotidase
  • Adenosine
  • Norepinephrine
Topics
  • 5'-Nucleotidase (metabolism)
  • Adenosine (metabolism, physiology)
  • Animals
  • Hydroxyl Radical (metabolism)
  • Microdialysis
  • Myocardial Ischemia (prevention & control)
  • Myocardial Reperfusion Injury (prevention & control)
  • Myocardium (metabolism)
  • Norepinephrine (physiology)
  • Potassium Channels (metabolism)
  • Rats

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