多非替利衍生物CPU228(V03) 对大鼠心室肌细胞钙瞬变的调节

中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (2): 121-127.

• 研究原著 • 下一篇

多非替利衍生物CPU228(V03) 对大鼠心室肌细胞钙瞬变的调节

黄志江, 林生, 戴德哉, 纳涛, 吉民¹, 赵小辰², 孙立²

中国药科大学药理研究室, ¹新药研究中心, ²新中新药筛选中心, 南京210009, 江苏

收稿日期:2004-10-21 修回日期:2005-01-07 出版日期:2005-02-06 发布日期:2020-11-18
通讯作者: 戴德哉, 男, 教授, 博士生导师, 研究方向:心血管药理学。Tel:025-83271270 E-mail:dezaidai@vip.sina.com
作者简介:黄志江, 男, 博士研究生, 研究方向:心血管药理学。Tel:025-83271453 E-mail:kuangzj@tom.com
基金资助:
国家自然科学基金重大项目资助(No30230170);江苏省苏科计(2000)173 号文资助。

Regulation effects of CPU 228 on cytosolic Ca²⁺ concentration and parameters of Ca²⁺ transients in rat myocardium during β-adrenergic stimulation

HUANG Zhi-jiang, LIN Sheng, DAI De-zai, NA Tao, JI Min¹, ZHAO Xiao-chen², Sun Li²

Institute of Pharmacology, ¹Center for Drug Research, ²Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, Jiangsu, China

Received:2004-10-21 Revised:2005-01-07 Online:2005-02-06 Published:2020-11-18

摘要/Abstract

摘要： 目的:在β-受体激动情况下, 研究多非替利衍生物CPU 228 对电刺激触发心肌细胞的胞浆Ca²⁺浓度([Ca²⁺]_i) 变化及钙瞬变动力学参数的影响。方法:游离单个大鼠心室肌细胞, Fluo-3/AM 负载, 电刺激诱发心室肌细胞钙瞬变, 定量测定心室肌细胞内Ca²⁺浓度变化, 异丙肾上腺素(isoproterenol, ISO) 100 nmol°L^-1激动β-受体, 观察CPU 228 1 μmol°L^-1对钙瞬变动力学参数、[Ca²⁺]_i 及钙负荷水平的影响。结果:CPU228 1 μmol°L^-1对大鼠心室肌细胞[Ca²⁺]_i 的影响不明显(P>0.05);ISO 100 nmol°L^-1显著升高大鼠心室肌细胞[Ca²⁺]_i 和细胞内钙负荷水平, 缩短钙瞬变时程, 并且增加钙瞬变的消除速率。CPU 2281 μmol°L^-1显著抑制ISO 的上述作用。结论:在β-受体激动情况下, CPU 228 可以降低心肌细胞[Ca²⁺]_i,使ISO 改变的钙瞬变动力学参数恢复到正常水平。

关键词: CPU228, 心室肌细胞, 异丙肾上腺素, 钙瞬变, Fluo-3

Abstract: AIM: To investigate the effects of CPU 228 on cytosolic Ca²⁺ concentration ([Ca²⁺]_i) and the parameters of Ca²⁺ transients in myocardium during β-adrenergic stimulation.METHODS: The cytosolic Ca²⁺ concentration of the isolated rat ventricular myocytes was measured by Fluo-3/AM.The Ca²⁺ transient of myocytes was twitched by 0.5 Hz field stimulation.Isoproterenol (ISO) 100 nmol°L^-1 was used for stimulate the β-adrenoceptor. The effects of CPU 228 1 μmol°L^-1 on [Ca²⁺]_i, the intracellular Ca²⁺ load level, Ca²⁺ transient duration and decay ratio was observed.RESULTS: ISO 100 nmol°L^-1 significantly increased the [Ca²⁺]_i, intracellular Ca²⁺ load level, and the post-peak decay ratio of cytosolic Ca²⁺, but it reduced the Ca²⁺ peak duration of Ca²⁺ transients in isolated rat ventricular myocytes. CPU 228 1 μmol°L^-1 did not affect the [Ca²⁺]_i in isolated rat ventricular myocytes, but it significantly restored the ISO-induced changes of [Ca²⁺]_i and Ca²⁺ transients to control level in concentration-dependent manner.CONCLUSION: CPU 228 can inhibit the increase of [Ca²⁺]_i, and restore the changed Ca²⁺ transients to control level during β-adrenergic stimulation. These effects of CPU 228 maybe due to its blockade of β-adrenoceptor or relate to its signal pathway and inhibition of the hyperphosphorylation effects.

Key words: CPU 228, ventricular myocytes, isoproterenol, Ca²⁺ transients, Fluo-3

中图分类号:

R966

黄志江, 林生, 戴德哉, 纳涛, 吉民, 赵小辰, 孙立. 多非替利衍生物CPU228(V03) 对大鼠心室肌细胞钙瞬变的调节[J]. 中国临床药理学与治疗学, 2005, 10(2): 121-127.

HUANG Zhi-jiang, LIN Sheng, DAI De-zai, NA Tao, JI Min, ZHAO Xiao-chen, Sun Li. Regulation effects of CPU 228 on cytosolic Ca²⁺ concentration and parameters of Ca²⁺ transients in rat myocardium during β-adrenergic stimulation[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(2): 121-127.

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多非替利衍生物CPU228(V03) 对大鼠心室肌细胞钙瞬变的调节

Regulation effects of CPU 228 on cytosolic Ca²⁺ concentration and parameters of Ca²⁺ transients in rat myocardium during β-adrenergic stimulation

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多非替利衍生物CPU228(V03) 对大鼠心室肌细胞钙瞬变的调节

Regulation effects of CPU 228 on cytosolic Ca2+ concentration and parameters of Ca2+ transients in rat myocardium during β-adrenergic stimulation

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Regulation effects of CPU 228 on cytosolic Ca²⁺ concentration and parameters of Ca²⁺ transients in rat myocardium during β-adrenergic stimulation