Intermedin (adrenomedullin-2): a novel counter-regulatory peptide in the cardiovascular and renal systems
Intermedin (adrenomedullin-2): a novel counter-regulatory peptide in the cardiovascular and renal systems
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DOI：
10.1038/sj.bjp.0707494
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发表时间：
2008-03-01
影响因子：
7.3
通讯作者：
McDermott, B. J.
中科院分区：
文献类型：
--
作者：
Bell, D.;McDermott, B. J.
中间肽（IMD）是一种与降钙素基因相关肽（CGRP）和肾上腺髓质素（AM）相关的新肽。较大前体的蛋白水解加工产生一系列具有生物活性的C-末端片段，IMD 1 -53、IMD 1 -47和IMD 8 -47。IMD与AM和CGRP共有一个受体家族，由降钙素受体样受体（CALCRL）和三种受体活性修饰蛋白（RAMP）之一组成。与CGRP相比，IMD对CGRP（1）受体的效力较低，但对AM（1）受体和AM（2）受体的效力较高;与AM相比，IMD对CGRP 1受体的效力较高，但对AM（1）和AM（2）受体的效力较低。IMD的细胞和组织分布在某些方面与CGRP和AM重叠，但与两者不同。IMD存在于新生儿中，但在成人心脏和血管系统中不存在或稀疏表达，并且在血浆中以低水平存在。IMD在下丘脑、垂体和肾脏中的突出定位与在循环和水电解质稳态的中枢和外周调节中的生理作用一致。IMD是一种有效的全身和肺血管扩张剂，影响局部血流并增强心脏收缩力。IMD保护心肌免受与缺血再灌注损伤相关的氧化应激的有害影响，并直接对心肌细胞施加抗生长作用以对抗肥大刺激的影响。在肥大和缺血心肌中肽表达的稳健增加表明IMD作为心脏中的内源性反调节肽具有重要的保护作用。
Intermedin (IMD) is a novel peptide related to calcitonin gene-related peptide ( CGRP) and adrenomedullin ( AM). Proteolytic processing of a larger precursor yields a series of biologically active C-terminal fragments, IMD1-53, IMD1-47 and IMD8-47. IMD shares a family of receptors with AM and CGRP composed of a calcitonin-receptor like receptor (CALCRL) associated with one of three receptor activity modifying proteins ( RAMP). Compared to CGRP, IMD is less potent at CGRP(1) receptors but more potent at AM(1) receptors and AM(2) receptors; compared to AM, IMD is more potent at CGRP1 receptors but less potent at AM(1) and AM(2) receptors. The cellular and tissue distribution of IMD overlaps in some aspects with that of CGRP and AM but is distinct from both. IMD is present in neonatal but absent or expressed sparsely, in adult heart and vasculature and present at low levels in plasma. The prominent localization of IMD in hypothalamus and pituitary and in kidney is consistent with a physiological role in the central and peripheral regulation of the circulation and water-electrolyte homeostasis. IMD is a potent systemic and pulmonary vasodilator, influences regional blood flow and augments cardiac contractility. IMD protects myocardium from the deleterious effects of oxidative stress associated with ischaemia-reperfusion injury and exerts an anti-growth effect directly on cardiomyocytes to oppose the influence of hypertrophic stimuli. The robust increase in expression of the peptide in hypertrophied and ischaemic myocardium indicates an important protective role for IMD as an endogenous counter-regulatory peptide in the heart.