Different roles of 
1-adrenoceptor subtypes in mediating cardiomyocyte protein synthesis in neonatal rats
Authors: Yongzhen Zhang; Jie Yan; Kai Chen1; Yao Song1; Zhizhen Lu1; Mingzhe Chen1; Chide Han1; Youyi Zhang1
Source: Clinical and Experimental Pharmacology and Physiology, Volume 31, Number 9, September 2004 , pp. 626-633(8)
Publisher: Blackwell Publishing
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Abstract:
Summary 1. Three different1-adrenoceptor subtypes, designated 1A, 1B and 1D, have been cloned and identified pharmacologically in cardiomyocytes. In vitro studies have suggested that 1-adrenoceptors play an important role in facilitating cardiac hypertrophy. However, it remains controversial as to which subtype of 1-adrenoceptors is involved in this response. In the present study, we investigated the different role of each 1-adrenoceptor subtype in mediating cardiomyocyte protein synthesis, which is a most important characteristic of cardiac hypertrophy in cultured neonatal rat cardiomyocytes. 2. Cardiomyocyte hypertrophy was monitored by the following characteristic phenotypic changes: (i) an increase in protein synthesis; (ii) an increase in total protein content; and (iii) an increase in cardiomyocyte size.3. The role of each 1-adrenoceptor subtype in mediating cardiomyocyte protein synthesis was investigated by the effect of specific 1-adrenoceptor subtype-selective antagonists on noradrenaline-induced [3H]-leucine incorporation. In addition, pKB values for 1-adrenoceptor subtype-selective antagonists were calculated and compared with the corresponding pKi values to further identify their effects. 4. Activation of 1-adrenoceptors by phenylephrine or noradrenaline in the presence of propranolol significantly increased [3H]-leucine incorporation, protein content and cell size. 5. Pre-incubating cardiomyocytes with 5-methyl-urapidil, RS 17053 or WB 4101 significantly inhibited noradrenaline-induced [3H]-leucine incorporation. However, there was no effect when cardiomyocytes were pre-incubated with BMY 7378. The correlation coefficients between pKB values for 1-adrenoceptor subtype-selective antagonists and pKi values obtained from cloned 1A-, 1B- or 1D-adrenoceptors were 0.92 (P < 0.01), 0.66 (P > 0.05) and 0.24 (P > 0.05), respectively. 6. Our results suggest that the 1-adrenoceptor is dominantly responsible for adrenergic hypertrophy of cultured cardiomyocytes in neonatal rats. The efficiency in mediating cardiomyocyte protein synthesis is 1A > 1B 
1D.
Keywords:
1-adrenoceptor;
cardiomyocytes;
hypertrophy;
protein synthesis;
subtype
Document Type: Research article
DOI: 10.1111/j.1440-1681.2004.04063.x
Affiliations: 1: Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, PR China
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