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- Title
Roles of K<sub>ATP</sub> channels in delayed cardioprotection and intracellular Ca<sup>2+</sup> in the rat heart as revealed by ?-opioid receptor stimulation with U50,488H.
- Authors
Mai Chen; Jing-Jun Zhou; Kenneth Wan-Lung Kam, Chris R.; Jian-Song Qi, Chris R.; Wing-Yi Yan, Chris R.; Song Wu; Tak-Ming Wong
- Abstract
1: The effect of preconditioning with U50,488?H (UP), a selective kappa-opioid receptor (?-OR) agonist, on infarct size and intracellular Ca2+ ([Ca2+]i) in the heart subjected to ischaemic insults were studied and evaluated. U50,488?H administered intravenously reduced the infarct size 18-48?h after administration in isolated hearts subjected to regional ischaemia/reperfusion (I/R). The effect was dose dependent. A peak effect was reached at 10?mg?kg-1 U50,488?H and at 24?h after administration. The effect of 10?mg?kg-1 U50,488?H at 24?h after administration was abolished by nor-binaltorphimine (nor-BNI), a selective ?-OR antagonist, indicating the effect was ?-OR mediated. 2: The infarct reducing effect of U50,488?H was attenuated when a selective blocker of mitochondrial (5-hydroxydecanoic acid, 5-HD) or sarcolemmal (HRM-1098) ATP-sensitive potassium channel (KATP) was coadministered with U50,488?H 24?h before ischaemia or when 5-HD was administered just before ischaemia. 3: U50,488?H also attenuated the elevation in [Ca2+]i and reduction in electrically induced [Ca2+]i transient in cardiomyocytes subjected to ischaemic insults. The effects were reversed by blockade of KATP channel, which abolished the protective effect of preconditioning with U50,488?H. 4: The results indicated that mitochondrial KATP channel serves as both a trigger and a mediator, while sarcolemmal KATP channel as a trigger only, of delayed cardioprotection of ?-OR stimulation. The effects of these channels may result from prevention/attenuation of [Ca2+]i overload induced by ischaemic insults.British Journal of Pharmacology (2003) 140, 750-758. doi:10.1038/sj.bjp.0705475
- Subjects
OPIOID receptors; ADENOSINE triphosphate; POTASSIUM channels; ISCHEMIA; REPERFUSION injury; HYPOXEMIA
- Publication
British Journal of Pharmacology, 2003, Vol 140, Issue 4, p750
- ISSN
0007-1188
- Publication type
Article
- DOI
10.1038/sj.bjp.0705475