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Role of 5-HT 2B Receptors in Cardiomyocyte Apoptosis in Noradrenaline-Induced Cardiomyopathy in Rats

Role of 5-HT 2B Receptors in Cardiomyocyte Apoptosis in Noradrenaline-Induced Cardiomyopathy in Rats

Chong-Feng Bai, Jin-Cheng Liu, Rong Zhao, Wei Cao, Shui-Bin Liu, Xiao-Nan Zhang, Hong-Ju Guo, Qi Yang, Ding-Hua Yi, Ming-Gao Zhao

Clin Exp Pharmacol Physiol. 2010 Jul;37(7):e145-51.

PMID: 20374255

Abstract:

1. Serotonin (5-hydroxytryptamine; 5-HT) plays important roles in the development of cardiac hypertrophy via activation of 5-HT receptors. The aim of the present study was to investigate the role of 5-HT(2B) receptors in the development of cardiomyocyte apoptosis and hypertrophy associated with noradrenaline (NA) overload. 2. Cardiac hypertrophy was induced in rats by intraperitoneal injection of 1.5 mg/kg NA for 4 weeks. Starting from Day 15, 5-HT2B receptor antagonist SB 204741 (i.p., 0.5 or 2 mg/kg) or SDZ SER 082 (i.p., 1 mg/kg) was injected twice daily for another 14 days. Whole-cell patch-clamp techniques were used to record ionic currents in freshly isolated ventricular cardiomyocytes. Western blot and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) assays were used to assess myocardial apoptosis. 3. Expression of 5-HT(2B) receptors was enhanced in the hypertrophic left ventricle induced by NE overload in vivo. The 5-HT(2B) receptor antagonist SB 204741 partially reversed cardiac hypertrophy induced by NE overload (P < 0.05) and decreased L-type calcium currents in ventricular cardiomyocytes (P < 0.05). In addition, SB 204741 notably attenuated myocardial apoptosis, as evidenced by downregulation of Bax and caspase 3 (P < 0.05) and upregulation of the anti-apoptotic Bcl-2 protein (P < 0.05). 4. In conclusion, the data suggest an involvement of 5-HT(2B) receptors in the generation of apoptotic events associated with cardiac remodelling during increased adrenergic stimulation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP152239468	SB 204741		152239-46-8	Price

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