Prior activation of protein kinase C (PKC) can precondition the cardiac cell against injury during subsequent ischaemia. By using cultured chick ventricular cell model for simulated ischaemia and preconditioning, the present study investigated the biochemical mechanism underlying the PKC-mediated preconditioning. A 5 min exposure to PMA enhanced the ability of pinacidil to mediate cardioprotection during a subsequent 90 min period of ischaemia, which is consistent with a sustained activation of the KATP channel initiated by PKC. The brief prior exposure to PMA was also associated with an enhanced ability of the adenosine A1 or A3 receptor agonist 2-chloro-N6-cyclopentyladenosine or N6-(3-iodobenzyl)adenosine-5´-N-methyluronamide to elicit a cardioprotective response during the subsequent ischaemia. In myocytes pretreated with PMA, the cardioprotection mediated by receptor agonist was blocked by the concomitant presence of KATP-channel antagonists glibenclamide or 5-hydroxydecanoic acid during the ischaemia. Thus the KATP channel acts downstream of the adenosine A1 and A3 receptors in mediating the protective effect due to prior PMA exposure. KATP channel activation is responsible for the adenosine receptor-mediated effect. PMA treatment had no effect on other A1 or A3 receptor-mediated effects such as the inhibition of adenylate cyclase, ruling out a direct stimulation of the receptor or G-protein by PMA. The present results indicate that prior stimulation of PKC causes a sustained KATP channel activation, which in turn renders the myocyte more responsive to the protective action of adenosine A1 and A3 receptor agonists during the subsequent ischaemia.
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Research Article| December 01 1998
Protein kinase C-dependent activation of KATP channel enhances adenosine-induced cardioprotection
Bruce T. LIANG
Bruce T. LIANG 1
1Department of Medicine, Cardiovascular Division, and Pharmacology, 504 Johnson Pavilion, University of Pennsylvania Medical Center, 3610 Hamilton Walk, Philadelphia, PA 19104, U.S.A.
1E-mail address firstname.lastname@example.org.
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Bruce T. LIANG; Protein kinase C-dependent activation of KATP channel enhances adenosine-induced cardioprotection. Biochem J 1 December 1998; 336 (2): 337–343. doi: https://doi.org/10.1042/bj3360337
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