title: Reciprocal regulation between M3 muscarinic acetylcholine receptor and protein kinase C-epsilon in ventricular myocytes during myocardial ischemia in rats.
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.
authors.affiliation: 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.
authors.forename: Peng-zhou
authors.initials: PZ
authors.lastname: Hang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Yu-ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Li-hua
authors.initials: LH
authors.lastname: Sun
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li-li
authors.initials: LL
authors.lastname: Yang
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.forename: Zhi-dan
authors.initials: ZD
authors.lastname: Sun
authors.forename: Yu-ying
authors.initials: YY
authors.lastname: Mao
authors.forename: Zhi-min
authors.initials: ZM
authors.lastname: Du
mesh_terms: 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
chemical_list: D043587:Receptor, Muscarinic M3; D051744:Protein Kinase C-epsilon
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