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| Content Provider | PubMed Central |
|---|---|
| Author | Node, Koichi Kitakaze, Masafumi Minamino, Tetsuo Tada, Michihiko Inoue, Michitoshi Hori, Masatsugu Kamada, Takenobu |
| Copyright Year | 1997 |
| Abstract | Ischaemic preconditioning (IP) protects the myocardium against irreversible ischaemic injury by activating protein kinase C (PKC). The mechanism by which PKC protects the myocardium is unknown. We have shown that PKC increases the activity of ecto-5′-nucleotidase (ecto-5′-N) and thereby the production of adenosine in cardiomyocytes which may protect the myocardium against ischaemia-reperfusion injury in vivo. The objective of this study was to elucidate the possible role of PKC-induced activation of ecto-5′-N in the cardioprotection associated with IP in the canine heart. IP increased the activities of both ecto-5′-N and PKC, and minimized ischaemic damage (infarct size: 7.5±1.8 vs. 42.3±2.8%, P<0.01 vs. the control group). Treatment with the PKC activator (4β-phorbol 12-myristate-13-acetate) also reduced infarct size (13.5±2.9%, P<0.01 vs. the control group). 8-Sulfophenyltheophylline (an antagonist of adenosine receptors) or α,β-methyleneadenosine 5′-diphosphate (an inhibitor of ecto-5′-N) eliminated the cardioprotective effect of the PKC activator (infarct size: 36.6±3.9 and 34.7±4.2%, respectively), suggesting that PMA limits infarct size by increasing the activity of ecto-5′-N and the adenosine level. The PMA-induced cardioprotection was blunted by GF109203X (an inhibitor of PKC, infarct size: 36.2±3.1%), but not by pretreatment with dexamethasone (infarct size, 14.2±2.6%). We conclude that the PMA- and IP-induced cardioprotection is attributable to phosphorylation and activation of ecto-5′-N. |
| Related Links | http://dx.doi.org/10.1038/sj.bjp.0700890 |
| Ending Page | 281 |
| Page Count | 9 |
| Starting Page | 273 |
| File Format | |
| ISSN | 00071188 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 120 |
| Language | English |
| Publisher Date | 1997-01-01 |
| Access Restriction | Open |
| Subject Keyword | Pharmacology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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