The pathophysiological role of adrenomedullin in septic lung models

点击翻译按钮获取中文摘要

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.