Intermedin (adrenomedullin-2) enhances cardiac contractile function via a protein kinase C- and protein kinase A-dependent pathway in murine ventricular myocytes
Intermedin (adrenomedullin-2) enhances cardiac contractile function via a protein kinase C- and protein kinase A-dependent pathway in murine ventricular myocytes
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DOI：
10.1152/japplphysiol.01631.2005
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发表时间：
2006-09-01
影响因子：
3.3
通讯作者：
Ren, Jun
中科院分区：
文献类型：
--
作者：
Dong, Feng;Taylor, Meghan M.;Ren, Jun
中间肽（IMD），也称为肾上腺髓质素-2，是来自降钙素基因相关肽（CGRP）/肾上腺髓质素肽家族的47个氨基酸的肽。最近的研究表明，IMD可能参与心血管功能和水电解质稳态的调节。为探讨IMD对心肌细胞收缩功能的影响，采用电起搏的方法，将小鼠心室肌细胞急性暴露于IMD中，测定以下指标：峰值缩短（PS）、达到PS的时间、达到90%再长的时间、最大缩短和再长速度。用fura 2-AM荧光显微镜测定细胞内Ca ~（2+）。我们的研究结果表明，IMD（10 pM至10 nM）显着增加PS和最大速度的缩短和再延长的心室肌细胞，其最大效果（类似于46%）是由CGRP（1 nM）和肾上腺髓质素（100 nM）引起的。IMD暴露显著缩短了至90%再充盈的时间，而不影响至PS的时间，与CGRP和肾上腺髓质素相似。IMD还促进细胞内Ca 2+释放，最大增加接近50%，并促进细胞内Ca 2+衰减速率。通过蛋白激酶C抑制剂白屈菜红碱（1 μ M）、使用佛波醇12-肉豆蔻酸酯13-乙酸酯（1 μ M）下调蛋白激酶C和蛋白激酶A抑制剂H89（1 μ M）消除IMD诱导的作用。我们的数据表明，IMD急性增强心肌细胞的收缩功能，至少部分，通过蛋白激酶C和蛋白激酶A依赖的机制。
Intermedin (IMD), also called adrenomedullin-2, is a 47-amino acid peptide from the calcitonin gene-related peptide (CGRP)/adrenomedullin family of peptides. Recent studies suggest that IMD may participate in the regulation of cardiovascular function and fluid and electrolyte homeostasis. To evaluate the role of IMD on cardiomyocyte contractile function, electrically paced murine ventricular myocytes were acutely exposed to IMD, and the following indexes were determined: peak shortening ( PS), time to PS, time-to-90% relengthening, and maximal velocity of shortening and relengthening. Intracellular Ca2+ was assessed using fura 2-AM fluorescent microscopy. Our results revealed that IMD (10 pM to 10 nM) significantly increased PS and maximal velocity of shortening and relengthening in ventricular myocytes, the maximal effect of which (similar to 46%) was somewhat comparable to those elicited by CGRP ( 1 nM) and adrenomedullin ( 100 nM). Exposure of IMD significantly shortened time-to-90% relengthening without affecting time to PS, similar to CGRP and adrenomedullin. IMD also enhanced intracellular Ca2+ release, with a maximal increase of similar to 50%, and facilitated the intracellular Ca2+ decay rate. The IMD-induced effects were abolished by the protein kinase C inhibitor chelerythrine ( 1 mu M), downregulation of protein kinase C using phorbol 12-myristate 13-acetate (1 mu M), and the protein kinase A inhibitor H89 (1 mu M). Our data suggest that IMD acutely augments cardiomyocyte contractile function through, at least in part, a protein kinase C-and protein kinase A-dependent mechanism.