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IR@PKUHSC  > 北京大学第三临床医学院  > 心血管内科  > 期刊论文
学科主题: 临床医学
题名:
Different roles of alpha(1)-adrenoceptor subtypes in mediating cardiomyocyte protein synthesis in neonatal rats
作者: Zhang, YZ1; Yan, J1; Chen, K1; Song, Y1; Lu, ZZ1; Chen, MZ1; Han, C1; Zhang, YY1
关键词: alpha(l)-adrenoceptor ; cardiomyocytes ; hypertrophy ; protein synthesis ; subtype
刊名: CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
发表日期: 2004-09-01
卷: 31, 期:9, 页:626-633
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy ; Physiology
研究领域[WOS]: Pharmacology & Pharmacy ; Physiology
关键词[WOS]: MYOCARDIAL-CELL HYPERTROPHY ; INDUCED CARDIAC-HYPERTROPHY ; TRANSGENIC MICE ; ALPHA(1B)-ADRENERGIC RECEPTORS ; MESSENGER-RNAS ; ALPHA-1-ADRENERGIC RECEPTOR ; INOTROPIC RESPONSES ; SIGNALING PATHWAYS ; KINASE CASCADE ; IN-VIVO
英文摘要:

1. Three different alpha(1)-adrenoceptor subtypes, designated alpha(1A), alpha(1B) and alpha(1D), have been cloned and identified pharmacologically in cardiomyocytes. In vitro studies have suggested that alpha(1)-adrenoceptors play an important role in facilitating cardiac hypertrophy. However, it remains controversial as to which subtype of alpha(1)-adrenoceptors is involved in this response. In the present study, we investigated the different role of each alpha(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 alpha(1)-adrenoceptor subtype in mediating cardiomyocyte protein synthesis was investigated by the effect of specific alpha(1)-adrenoceptor subtype-selective antagonists on noradrenaline-induced [H-3]-leucine incorporation. In addition, pK(B) values for alpha(1)-adrenoceptor subtype-selective antagonists were calculated and compared with the corresponding pK(i) values to further identify their effects.

4. Activation of alpha(1)-adrenoceptors by phenylephrine or noradrenaline in the presence of propranolol significantly increased [H-3]-leucine incorporation, protein content and cell size.

5. Pre-incubating cardiomyocytes with 5-methyl-urapidil, RS 17053 or WB 4101 significantly inhibited noradrenaline-induced [H-3]-leucine incorporation. However, there was no effect when cardiomyocytes were pre-incubated with BMY 7378. The correlation coefficients between pK(B) values for alpha(1)-adrenoceptor subtype-selective antagonists and pK(i) values obtained from cloned alpha(1A)-, alpha(1B)- or alpha(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 alpha(1)-adrenoceptor is dominantly responsible for adrenergic hypertrophy of cultured cardiomyocytes in neonatal rats. The efficiency in mediating cardiomyocyte protein synthesis is alpha(1A) > (alpha(1B) much greater than alpha(1D).

语种: 英语
WOS记录号: WOS:000224248600011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52869
Appears in Collections:北京大学第三临床医学院_心血管内科_期刊论文

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作者单位: 1.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China
2.Peking Univ, Hosp 3, Inst Vasc Med, Beijing 100083, Peoples R China

Recommended Citation:
Zhang, YZ,Yan, J,Chen, K,et al. Different roles of alpha(1)-adrenoceptor subtypes in mediating cardiomyocyte protein synthesis in neonatal rats[J]. CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY,2004,31(9):626-633.
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