Dong Feng, Taylor Meghan M, Samson Willis K, Ren Jun
Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071-3375, USA.
J Appl Physiol (1985). 2006 Sep;101(3):778-84. doi: 10.1152/japplphysiol.01631.2005. Epub 2006 Jun 8.
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 Ca(2+) 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 (approximately 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 Ca(2+) release, with a maximal increase of approximately 50%, and facilitated the intracellular Ca(2+) decay rate. The IMD-induced effects were abolished by the protein kinase C inhibitor chelerythrine (1 microM), downregulation of protein kinase C using phorbol 12-myristate 13-acetate (1 microM), and the protein kinase A inhibitor H89 (1 microM). 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.
中介素（IMD），也称为肾上腺髓质素-2，是一种由47个氨基酸组成的肽，属于降钙素基因相关肽（CGRP）/肾上腺髓质素肽家族。最近的研究表明，IMD可能参与心血管功能以及体液和电解质稳态的调节。为了评估IMD对心肌细胞收缩功能的作用，将电刺激的小鼠心室肌细胞急性暴露于IMD，并测定以下指标：峰值缩短（PS）、达到PS的时间、90%再延长时间以及缩短和再延长的最大速度。使用fura 2-AM荧光显微镜评估细胞内Ca(2+)。我们的结果显示，IMD（10 pM至10 nM）显著增加心室肌细胞的PS以及缩短和再延长的最大速度，其最大效应（约46%）在某种程度上与CGRP（1 nM）和肾上腺髓质素（100 nM）所引发的效应相当。与CGRP和肾上腺髓质素相似，IMD暴露显著缩短90%再延长时间，而不影响达到PS的时间。IMD还增强细胞内Ca(2+)释放，最大增加约50%，并促进细胞内Ca(2+)衰减率。蛋白激酶C抑制剂白屈菜红碱（1 microM）、使用佛波酯12-肉豆蔻酸酯13-乙酸酯（1 microM）下调蛋白激酶C以及蛋白激酶A抑制剂H89（1 microM）可消除IMD诱导的效应。我们的数据表明，IMD至少部分通过蛋白激酶C和蛋白激酶A依赖性机制急性增强心肌细胞收缩功能。
