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学科主题: 基础医学
题名:
Receptor subtype involved in alpha(1)-adrenergic receptor-mediated Ca2+ signaling in cardiomyocytes
作者: Luo, Da-li; Gao, Jian; Fan, Lin-lin; Tang, Yu; Zhang, You-yi; Han, Qi-de
关键词: alpha(1)-adrenergic receptor ; subtype ; cardiomyocyte ; Ca2+ signaling ; A61603
刊名: ACTA PHARMACOLOGICA SINICA
发表日期: 2007-07-01
DOI: 10.1111/j.1745-7254.2007.00605.x
卷: 28, 期:7, 页:968-974
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]: Chemistry ; Pharmacology & Pharmacy
关键词[WOS]: INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS ; RAT VENTRICULAR MYOCYTES ; ALPHA(1C)-ADRENERGIC RECEPTOR ; CARDIAC MYOCYTES ; ALPHA(1B)-ADRENERGIC RECEPTORS ; ALPHA(1A) SUBTYPE ; KNOCKOUT MOUSE ; MESSENGER-RNAS ; HYPERTROPHY ; HEARTS
英文摘要:

Aim: The enhancement of intracellular Ca2+ signaling in response to alpha(1)-adrenergic receptor (alpha(1)-AR) stimulation is an essential signal transduction event in the regulation of cardiac functions, such as cardiac growth, cardiac contraction, and cardiac adaptation to various situations. The present study was intended to determine the role(s) of the alpha(1)-AR subtype(s) in mediating this response.

Methods: We evaluated the effects of subtype-specific agonists and antagonists of the alpha(1)-AR on the intracellular Ca2+ signaling of neonatal rat ventricular myocytes using a confocal microscope.

Results: After being cultured for 48 h, the myocytes exhibited spontaneous local Ca2+ release, sparks, and global Ca2+ transients. The activation of the alpha(1)-AR with phenylephrine, a selective agonist of the alpha(1)-AR, dose-dependently increased the frequency of Ca2+ transients with an EC50 value of 2.3 mu mol/L. Blocking the alpha(1A)-AR subtype with 5-methylurapidil (5-Mu) inhibited the stimulatory effect of phenylephrine with an IC50 value of 6.7 nmol/L. In contrast, blockade of the alpha(1B)-AR and alpha(1D)-AR subtypes with chlorethylclonidine and BMY 7378, respectively, did not affect the phenylephrine effect. Similarly, the local Ca2+ spark numbers were also increased by the activation of the alpha(1)-AR, and this effect could be abolished selectively by 5-Mu. More importantly, A61603, a novel selective alpha(1A)-AR agonist, mimicked the effect of phenylephrine, but with more potency (EC50 value=6.9 nmol/L) in the potentiation of Ca2+ transients, and blockade of the alpha(1A)-AR by 5-Mu caused abolishment of its effects.

Conclusion: These results indicate that alpha(1)-adrenergic stimulation of intracellular Ca2+ activity is mediated selectively by the alpha(1A)-AR.

语种: 英语
WOS记录号: WOS:000247661400007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65864
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.Capital Univ Med Sci, Sch Chem Biol & Pharmaceut Sci, Dept Pharmacol, Beijing 100069, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100083, Peoples R China

Recommended Citation:
Luo, Da-li,Gao, Jian,Fan, Lin-lin,et al. Receptor subtype involved in alpha(1)-adrenergic receptor-mediated Ca2+ signaling in cardiomyocytes[J]. ACTA PHARMACOLOGICA SINICA,2007,28(7):968-974.
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