The pathophysiological role of adrenomedullin in septic lung models

肾上腺髓质素(AM)是一种多功能多肽，1993年从人嗜铬细胞瘤的酸性提取物中检测到血小板中环磷酸腺苷(CAMP)的增加而分离出来。AM在结构上类似于降钙素基因相关肽(CGRP)，CGRP是一种有效的血管扩张肽。因此，AM被归类为CGRP超家族的成员。McLatchie等人。据报道，AM和CGRP的受体由降钙素受体样受体(CRLR)和受体活性修饰蛋白(RAMPS)两部分组成。到目前为止，CRLR一直被认为是CGRP的受体。他们提到，RAMPS对CRLR进行了修改，使其专用于AM或CGRP。RAMP有三种表型：RAMP 1、RAM2和RAM3。据报道，CRLR分别与RAMP1和2或3共表达时形成CGRP和AM的特异性受体。虽然CRLR在几乎所有组织中都有表达，但CRLR基因在正常小鼠的肺中表达最高。在Northern杂交分析中，RAMP1在脑和胸腺中检测到高密度条带，RAMP2在肺中检测到高密度条带，RAMP3在脑和肾脏中检测到高密度条带。坡道的分布应决定AM的生理意义此外，CRLR和RAMPS的表达模式在脓毒症或肾炎中也有改变。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。

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.