Identification of novel adrenomedullin in mammals: a potent cardiovascular and renal regulator

FEBS Letters

Miyano, Satoru²  Kawahara, Tetsushi³  Bannai, Hideo²  Takei, Yoshio¹  Inoue, Koji¹  Ogoshi, Maho¹ 

[1] Laboratory of Physiology, Department of Marine Bioscience, Ocean Research Institute, University of Tokyo, 1-15-1 Minamidai, Nakano-ku, Tokyo 164-8639, Japan;Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan;Pharmaceutical Research Center Discovery Research III, Mochida Pharmaceutical Co. Ltd., Gotenba, Shizuoka 412-8524, Japan

关键词: Calcitonin gene-related peptide family;    Adrenomedullin family;    Vasodepressor action;    Antidiuretic action;    Comparative genomics;    Molecular evolution;   

DOI  :  10.1016/S0014-5793(03)01368-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have identified cDNA encoding a new member of the adrenomedullin (AM) family, AM2, for the first time in mammals (mouse, rat and human). The predicted precursor carried mature AM2 in the C-terminus, which had an intramolecular ring formed by an S–S bond and a possibly amidated C-terminus. Phylogenetic analyses clustered AM2 and AM into two distinct but closely related groups. Similarity of exon–intron structure and synteny of neighboring genes showed that mammalian AM2 is an ortholog of pufferfish AM2 and a paralog of mammalian AM. AM2 mRNA was expressed in submaxillary gland, kidney, stomach, ovary, lymphoid tissues and pancreas of mice, but not in adrenal and testis. Intravenous injection of synthetic mature AM2 decreased arterial pressure more potently than AM, and induced antidiuresis and antinatriuresis in mice. These results show that at least two peptides, AM and AM2, comprise an adrenomedullin family in mammals, and that AM2 may play pivotal roles in cardiovascular and body fluid regulation.

【 授权许可】

Unknown