Evidence for MOR on cell membrane, sarcoplasmatic reticulum and mitochondria in left ventricular myocardium in rats
Evidence for MOR on cell membrane, sarcoplasmatic reticulum and mitochondria in left ventricular myocardium in rats
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MOR 对大鼠左心室心肌细胞膜、肌浆网和线粒体的影响的证据
DOI：
10.1007/s00380-015-0784-8
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发表时间：
2016
影响因子：
1.5
通讯作者：
Mousa SA
中科院分区：
文献类型：
--
作者：
Treskatsch S;Shaqura M;Dehe L;Roepke TK;Shakibaei M;Schäfer M;Mousa SA
心脏功能是维持组织氧合的一个重要决定因素，因此受到高度调节。在这种情况下，有趣的是，中枢介导的阿片类药物对心脏功能的影响早已众所周知。直到最近，才发现KOR和DOR在大鼠健康左心室心肌中表达，并与部分兴奋-收缩-偶联系统共定位。然而，文献中的一些评论怀疑心脏组织中存在莫尔。因此，我们的目的是检测大鼠左心室心肌细胞的莫尔，并评估莫尔和POMC是否在心力衰竭过程中受到调节。IRB批准后，在雄性Wistar大鼠中使用改良的肾下下腔静脉瘘（ACF）诱导心力衰竭。对照组和ACF组大鼠进行形态计量学和血流动力学观察，并采用放射配基结合、免疫荧光共聚焦、RT-PCR和Western blot等方法检测莫尔和POMC的存在。在左心室心肌中检测到膜莫尔选择性结合位点，但其丰度低于KOR和DOR特异性结合位点，且无法测定莫尔的Bmax。在左心室心肌细胞中，莫尔与部分兴奋偶联机制共定位，例如，Cav1.2的细胞膜和内陷的T-小管，以及ryanodine受体的肌浆网。更重要的是，莫尔与左心室心肌细胞的线粒体强烈共定位。容量超负荷与莫尔和POMC在mRNA和蛋白水平上的表达改变无关。这些发现为大鼠左心室心肌细胞的细胞膜、肌浆网和线粒体上存在莫尔反应提供了证据。然而，心力衰竭不会导致心脏MOR-阿片系统的表达改变。因此，莫尔激动剂治疗-通常用于临床设置-可能会直接影响心脏功能，这需要在不久的将来进行更详细的评估。
Cardiac function is one important determinant to maintain tissue oxygenation and is thus highly regulated. In this context, it is interesting that centrally mediated opioidergic influence on cardiac function has long been known. Only recently, KOR and DOR have been found to be expressed in healthy left ventricular myocardium in rats and colocalized with parts of the excitation–contraction-coupling system. However, several comments in literature exist doubting the existence of MOR in cardiac tissue. We, therefore, aimed to detect MOR in rat left ventricular cardiomyocytes, and to evaluate whether MOR and POMC are regulated during heart failure. After IRB approval, heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. All rats of the control and ACF group were characterized by their morphometrics and hemodynamics and the existence of MOR and POMC was investigated by means of radioligand binding, double immunofluorescence confocal analysis, RT-PCR and Western blot. Membrane MOR selective binding sites were detected in the left ventricular myocardium, however, they were lower in abundance than KOR- and DOR-specific binding sites andBmaxof MOR could not be determined. In left ventricular cardiomyocytes, MOR colocalized with parts of the excitation-coupling mechanism, e.g., Cav1.2 of the cell membrane and invaginated T-tubules as well as the ryanodine receptor of the sarcoplasmatic reticulum. More importantly, MOR strongly colocalized with mitochondria of left ventricular cardiomyocytes. Volume overload was not associated with an altered expression of MOR and POMC on both mRNA and protein level. These findings provide evidence for the existence of MOR on the cell membrane, sarcoplasmatic reticulum and mitochondria in left ventricular cardiomyocytes in rats. However, heart failure does not result in an altered expression of the cardiac MOR-opioid system. Thus, MOR agonist treatment—commonly used in the clinical setting—might directly affect cardiac function, which needs to be evaluated in greater detail in the near future.
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吗啡可增强豚鼠完整跳动心脏中肌丝 CA(2) 的敏感性。
影响因子：
5.7
作者：
Y. Nakae;S. Fujita;A. Namiki
通讯作者：
A. Namiki
DOI：
--
发表时间：
2007-03
期刊：
Journal of the American Association for Laboratory Animal Science : JAALAS
影响因子：
--
作者：
D. Saha;Animita C. Saha;G. Malik;M. Astiz;E. Rackow
通讯作者：
D. Saha;Animita C. Saha;G. Malik;M. Astiz;E. Rackow
影响因子：
8.8
作者：
SHOEMAKER, WC;APPEL, PL;KRAM, HB
通讯作者：
KRAM, HB
吗啡通过肌细胞中的自由基信号和线粒体 KATP 通道模拟预处理
影响因子：
37.8
作者：
B. C. McPherson;Z. Yao
通讯作者：
Z. Yao
影响因子：
7.7
作者：
Mousa SA;Shaqura M;Khalefa BI;Zöllner C;Schaad L;Schneider J;Shippenberg TS;Richter JF;Hellweg R;Shakibaei M;Schäfer M
通讯作者：
Schäfer M