Molcular Mechanisms and Clinical Role of the Phosphorylation and Activation of Ecto-5'-Nucleotidase, Adenosine Producing Enzyme in Cardioprotection.

点击翻译按钮获取中文摘要

We have previously reported that activation of protein kinase C via α 1-adrenergic stimulation activates ecto-5'-nucleotidase, which produces adenosine. Therefore, we investigated whether the activation of ecto-5'-nucleotidase plays a role in cardioprotection in vivo via the adenosine production.First, we found that an intracoronary administration of ATP, metabolized rapidly to adenosine, reduces infarct size in canine hearts. We also establish the mice overexpressional model of ecto-5'-nucleotidase, and now under the examination on the molecular mechanisms for cardioprotection of ecto-5'-nucleotidase.Furthermore, we are now proceeding a clinical large-scale trial named COAT study to estimate the clinical impact of adenosine on cardioprotection. We have preliminarily reported this efficacy.Second, we found that AICA riboside, Na+/H+ exchanger inhibitors, and ATP-sensitive potassium channel openers can increase the activity of ecto-5'-nucleotidase. Since these compounds have the cardioprotective effect in canine model in vivo, we suggest the involvement of adenosine in the effects of these drugs.Third, we established that the pretreatment with nicotine has cardioprotecitive effects against myocardial necrosis and stunning via nicotinic receptor activation, and the α1-adrenoceptor activation, which increases ecto-5'-nucleotidase activity and enhances the regional adenine production (submitted).These basic and clinical evidence indicates the beneficial action of adenosine and ecto-5'-nucleotidase in cardiology.