M3 muscarinic acetylcholine receptor is associated with beta-catenin in ventricular myocytes during myocardial infarction in the rat.
1. The present study was designed to investigate whether the M(3) muscarinic acetylcholine receptors (mAChR) is associated with beta-catenin in the ventricular myocardium during ischaemic myocardial injury and to determine the possible mechanism/s involved. 2. Rat hearts were subjected to coronary artery ligation for 1 and 6 h or 1 month to establish a myocardial ischaemia (MI) model. In the acute MI model, 16 rats were randomized into four groups: (i) control; (ii) ischaemia (rats were subjected to 20 min coronary occlusion); (iii) choline (10 mg/kg, i.v., choline chloride, an M(3) receptor agonist, was administered 15 min before occlusion); and (iv) 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; 0.12 mg/kg 4-DAMP, an M(3) receptor antagonist, was administered 20 min before occlusion, followed 5 min later by 10 mg/kg, i.v., choline chloride). Immunochemistry, western blot analysis and immunoprecipitation were used to determine the expression and localization of beta-catenin and the M(3) mAChR. 3. Myocardial ischaemia caused a time-dependent increase in the expression of beta-catenin. Moreover, a physical association was found between beta-catenin and the M(3) mAChR in intercalated discs. This association was enhanced by prolonged ischaemia. Administration of choline before ischaemia not only increased beta-catenin expression, but also strengthened the association between beta-catenin and the M(3) mAChR. However, blockade of M(3) mAChR by 4-DAMP completely inhibited the effect of choline on the expression of beta-catenin. In addition, MI increased phosphorylation of the M(3) mAChR. 4. The results indicate that increased beta-catenin activity is associated with M(3) mAChR during MI. This association is likely to play a role in heart signal transduction during ischaemia between neighbouring ventricular myocardiocum.
Wang
Yu-Ping
YP
Institute of Clinical Pharmacology of Second Hospital, Harbin Medical University, Harbin, PR China.
Hang
Peng-Zhou
PZ
Sun
Li-Hua
LH
Zhang
Yong
Y
Zhao
Jin-Long
JL
Pan
Zhen-Wei
ZW
Ji
Hong-Rui
HR
Wang
Li-An
LA
Bi
Hui
H
Du
Zhi-Min
ZM
D000818:Animals; D002794:Choline / Q000494:pharmacology; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D014018:Tissue Distribution; D051176:beta Catenin / Q000378:metabolism*
D043587:Receptor, Muscarinic M3; D051176:beta Catenin; D002794:Choline