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学科主题: 基础医学
题名:
Role of inositol 1,4,5-trisphosphate receptors in alpha(1)-adrenergic receptor-induced cardiomyocyte hypertrophy
作者: Luo, DL; Gao, J; Lan, XM; Wang, G; Wei, S; Xiao, RP; Han, QD
关键词: inositol 1,4,5-trisphosphate receptors ; Ca2+ sparks ; alpha(1) adrenergic stimulation ; cardiac hypertrophy
刊名: ACTA PHARMACOLOGICA SINICA
发表日期: 2006-07-01
DOI: 10.1111/j.1745-7254.2006.00382.x
卷: 27, 期:7, 页:895-900
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]: PROTEIN-KINASE-C ; CALCIUM-RELEASE CHANNELS ; CARDIAC-HYPERTROPHY ; HEART-FAILURE ; MYOCARDIAL HYPERTROPHY ; TRANSCRIPTION FACTORS ; CALCINEURIN ; EXPRESSION ; G-ALPHA(Q) ; PATHWAY
英文摘要:

Aim: Intracellular Ca2+ plays pivotal roles in diverse cellular functions, including gene transcription that underlies cardiac remodeling during stress responses. However, the role of inositol 1,4,5-trisphosphate receptors (IP(3)Rs) in the mediation of cardiac intracellular Ca2+ and hypertrophic growth remains elusive. Prior work with neonatal rat ventricular myocytes suggests that activation of IP(3)Rs may be linked to alpha(1) adrenergic receptor (alpha(1) AR) increased stereotyped Ca2+ spark occurrence and global Ca2+ oscillations. Thus, we hypothesized that Ca2+ release through IP(3)Rs was necessary for alpha(1) AR-stimulated cardiac hypertrophy. Methods: We used myoinositol 1,4,5-trisphosphate hexakis (butyryloxymethyl) ester (IP3BM), a membrane-permeant ester of IP3, to activate IP(3)Rs directly, and Fluo 4/AM to measure intracellular Ca2+ signaling. Results: IP3BM (10 mu mol-L-1) mimicked the effects of phenylephrine, a selective agonist of alpha(1)AR, in increments in local Ca2+ spark release (especially in the perinuclear area) and global Ca2+ transient frequencies. More importantly, IP3R inhibitors, 2-aminoethoxydiphenyl borate and Xestospongin C, abolished the IP3BM-induced Ca2+ responses, and significantly suppressed alpha(1)AR-induced cardiomyocyte hypertrophy assayed by cell size, [H-3] leucine incorporation and atrial natriuretic factor gene expression, during sustained (48 h) phenylephrine stimulation. Conclusion: These results, therefore, provide cellular mechanisms that link IP3R signaling to alpha(1) AR-stimulated gene expression and cardiomyocyte hypertrophy.

语种: 英语
WOS记录号: WOS:000238485300017
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60651
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.Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China
2.Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China
3.Capital Univ Med Sci, Sch Chem Biol & Pharmaceut Sci, Dept Pharmacol, Beijing 100069, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100083, Peoples R China

Recommended Citation:
Luo, DL,Gao, J,Lan, XM,et al. Role of inositol 1,4,5-trisphosphate receptors in alpha(1)-adrenergic receptor-induced cardiomyocyte hypertrophy[J]. ACTA PHARMACOLOGICA SINICA,2006,27(7):895-900.
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