The pathophysiological role of adrenomedullin in septic lung models

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671624
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Hyogo College of Medicine
• Principal Investigator: OKANO Yukari (小野 紫) Hyogo College of Medicine, Research Associate, 医学部, 助手 (30312002)
• Co-Investigator(Kenkyū-buntansha): KANGAWA Kenji National Cardiovascular Center Research Insitute, 研究所, 部長 (00112417) ; OKANO Ichiro National Cardiovascular Center Research Insitute, 研究所, 室員 (30300974) ; OKUTANI Ryu Hyogo College of Medicine, Associate Professor, 医学部, 助教授 (90204122) ; TASHIRO Chikara Hyogo College of Medicine, Professor, 医学部, 教授 (20107048)
• Project Period (FY): 2001 – 2002
• Keywords: adrenomedullin / septic model / receptor / lung

Research Abstract

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.