Abstract
We have studied the association between M3 muscarinic acetylcholine receptors (M3-mAChR) and protein kinase C-ε (PKC-ε) during ischemic myocardial injury using Western blot analysis and immunoprecipitation technique. Myocardial ischemia (MI) induced PKC-ε translocation from cytosolic to membrane fractions. This translocation participated in the phosphorylation of M3-mAChR in membrane fractions, which could be abolished by the inhibitor of PKC, chelerythrine chloride. On the other hand, M3-mAChR could also regulate the expression of PKC-ε in ischemic myocardium. Choline (choline chloride, an M3 receptor agonist, administered at 15 min before occlusion) strengthened the association between PKC-ε and M3-mAChR. However, blockade of M3-mAChR by 4-diphenylacetoxy-N-methylpiperidine methiodide (an M3 receptor antagonist, administered at 20 min before occlusion) completely inhibited the effect of choline on the expression of PKC-ε. We conclude that the translocation of PKC-ε is required for the phosphorylation of M3-mAChR; moreover, increased PKC-ε activity is associated with M3-mAChR during MI. This reciprocal regulation is likely to play a role in heart signal transduction during ischemia between ventricular myocytes.
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Acknowledgement
This study was supported by grants from the National Natural Science Foundation of China (no. 30672462) and the Specialized Research Fund for the Doctoral Program of Higher Education (no. 20050226010).
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Hang, Pz., Zhao, J., Wang, Yp. et al. Reciprocal regulation between M3 muscarinic acetylcholine receptor and protein kinase C-ε in ventricular myocytes during myocardial ischemia in rats. Naunyn-Schmied Arch Pharmacol 380, 443–450 (2009). https://doi.org/10.1007/s00210-009-0444-6
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DOI: https://doi.org/10.1007/s00210-009-0444-6