[Adenosine production and its role in protection against ischemic and reperfusion injury of the myocardium].
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.
Obata
Toshio
T
Department of Pharmacology, Oita Medical University, 1-1, Hasama-machi, Oita 879-5593, Japan. tobata@oita-med.ac.jp
D015720:5'-Nucleotidase / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D017665:Hydroxyl Radical / Q000378:metabolism; D017551:Microdialysis; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats
D015221:Potassium Channels; D017665:Hydroxyl Radical; D015720:5'-Nucleotidase; D000241:Adenosine; D009638:Norepinephrine