Reciprocal regulation between M3 muscarinic acetylcholine receptor and protein kinase C-epsilon in ventricular myocytes during myocardial ischemia in rats.
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.
Hang
Peng-zhou
PZ
Institute of Clinical Pharmacology of Second Hospital, Harbin Medical University, Key Laboratory of Heilongjiang Province, Baojian Road 157, Nangang District, Harbin, Heilongjiang Province, 150081, People's Republic of China.
Zhao
Jing
J
Wang
Yu-ping
YP
Sun
Li-hua
LH
Zhang
Yong
Y
Yang
Li-li
LL
Zhao
Na
N
Sun
Zhi-dan
ZD
Mao
Yu-ying
YY
Du
Zhi-min
ZM
D000818:Animals; D015153:Blotting, Western; D047468:Immunoprecipitation; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010766:Phosphorylation; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D015398:Signal Transduction
D043587:Receptor, Muscarinic M3; D051744:Protein Kinase C-epsilon
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