Reciprocal regulation between M3 muscarinic acetylcholine receptor and protein kinase C-epsilon in ventricular myocytes during myocardial ischemia in rats.
Naunyn Schmiedebergs Arch Pharmacol
; 380(5): 443-50, 2009 Nov.
Article
in En
| MEDLINE
| ID: mdl-19685039
ABSTRACT
We have studied the association between M(3) muscarinic acetylcholine receptors (M(3)-mAChR) and protein kinase C-epsilon (PKC-epsilon) during ischemic myocardial injury using Western blot analysis and immunoprecipitation technique. Myocardial ischemia (MI) induced PKC-epsilon translocation from cytosolic to membrane fractions. This translocation participated in the phosphorylation of M(3)-mAChR in membrane fractions, which could be abolished by the inhibitor of PKC, chelerythrine chloride. On the other hand, M(3)-mAChR could also regulate the expression of PKC-epsilon in ischemic myocardium. Choline (choline chloride, an M(3) receptor agonist, administered at 15 min before occlusion) strengthened the association between PKC-epsilon and M(3)-mAChR. However, blockade of M(3)-mAChR by 4-diphenylacetoxy-N-methylpiperidine methiodide (an M(3) receptor antagonist, administered at 20 min before occlusion) completely inhibited the effect of choline on the expression of PKC-epsilon. We conclude that the translocation of PKC-epsilon is required for the phosphorylation of M(3)-mAChR; moreover, increased PKC-epsilon activity is associated with M(3)-mAChR during MI. This reciprocal regulation is likely to play a role in heart signal transduction during ischemia between ventricular myocytes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Myocardial Ischemia
/
Myocytes, Cardiac
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Receptor, Muscarinic M3
/
Protein Kinase C-epsilon
Limits:
Animals
Language:
En
Journal:
Naunyn Schmiedebergs Arch Pharmacol
Year:
2009
Document type:
Article