The pathophysiological role of adrenomedullin in septic lung models

肾上腺髓质素在脓毒症肺模型中的病理生理作用

• 批准号: 13671624
• 负责人: OKANO Yukari
• 金额: $ 2.56万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671624/
• 关键词: adrenomedullin; septic model; receptor; lung; アドレノメデュリン; 敗血症

Adrenomedullin (AM) is a multifunctional peptide that was isolated by monitoring increases in cyclic adenosine mono-phosphate (cAMP) in platelets from an acid extract of human pheochromocytoma in 1993. AM is structurally similar to calcitonin-gene-related peptide (CGRP), a potent vasodilating peptide. Thus, AM is classified as a member of the CGRP-superfamily. McLatchie et al. reported that the receptor for AM and CGRP consisted of two components, viz.calcitonin receptor-like receptor (CRLR) and receptor-activity modifying proteins (RAMPs). CRLR has been so far known as the receptor for CGRP. They mentioned that RAMPs modified CRLR to make it specific for AM or CGRP. Three phenotypes of RAMPs are now identified, RAMP 1,2 and 3. It was reported that CRLR formed specific receptors for CGRP and AM when coexpressed with RAMP1 and 2 or 3, respectively. Though CRLR is present in almost all tissues, the gene expression of CRLR was the highest in the lungs of normal mice. In the northern blot analysis, the high density of band of RAMP1 was detected in the brain and thymus, RAMP2 in the lungs, and RAMP3 in the brain and kidney. The distribution of RAMPs should determine the physiological meaning of AM. Furthermore, the expression patterns of CRLR and RAMPs were reported to changed in sepsis or renal nephritis. The fact may contribute to clarify the pathophysiological role of AM in these disease.

肾上腺髓质素（AM）是一种多功能肽，1993年通过监测血小板中环磷酸腺苷（cAMP）的增加从人嗜铬细胞瘤的酸提取物中分离出来。AM在结构上类似于降钙素基因相关肽（CGRP），一种有效的血管舒张肽。因此，AM被分类为CGRP超家族的成员。McLatchie等报道AM和CGRP的受体由两种成分组成，即降钙素受体样受体（CRLR）和受体活性修饰蛋白（RAMP）。迄今为止，CRLR被认为是CGRP的受体。他们提到RAMPs修饰CRLR使其特异于AM或CGRP。目前已鉴定出RAMP的三种表型，RAMP 1、2和3。CRLR分别与RAMP 1、2或3共表达时，可形成CGRP和AM的特异性受体。虽然CRLR存在于几乎所有组织中，但CRLR的基因表达在正常小鼠的肺中最高。在北方印迹分析中，RAMP 1在脑和胸腺中检测到高密度条带，RAMP 2在肺中检测到高密度条带，RAMP 3在脑和肾中检测到高密度条带。RAMPs的分布决定了AM的生理意义。此外，CRLR和RAMPs的表达模式在脓毒症或肾炎中有报道改变。这一事实可能有助于阐明AM在这些疾病中的病理生理作用。