TY - JOUR
T1 - Identification of novel adrenomedullin in mammals
T2 - A potent cardiovascular and renal regulator
AU - Takei, Yoshio
AU - Inoue, Koji
AU - Ogoshi, Maho
AU - Kawahara, Tetsushi
AU - Bannai, Hideo
AU - Miyano, Satoru
N1 - Funding Information:
The authors thank Dr. Christopher A. Loretz of the State University of New York at Buffalo for his comments on the manuscript, Ms. Sanae Hasegawa of the Ocean Research Institute for her excellent technical assistance, and Dr. Yoshitaka Oka and Ms. Miho Kyokuwa of the Graduate School of Science, University of Tokyo for their advice on mammal maintenance. This work was supported in part by Grants-in-Aid for Creative Basic Research (12NP0201) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and for Scientific Research (13304063) from the Japan Society for the Promotion of Science to Y.T.
PY - 2004/1/2
Y1 - 2004/1/2
N2 - 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.
AB - 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.
KW - Adrenomedullin family
KW - Antidiuretic action
KW - Calcitonin gene-related peptide family
KW - Comparative genomics
KW - Molecular evolution
KW - Vasodepressor action
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U2 - 10.1016/S0014-5793(03)01368-1
DO - 10.1016/S0014-5793(03)01368-1
M3 - Article
C2 - 14706825
AN - SCOPUS:0346094400
SN - 0014-5793
VL - 556
SP - 53
EP - 58
JO - FEBS Letters
JF - FEBS Letters
IS - 1-3
ER -