Identification of novel adrenomedullin in mammals: a potent cardiovascular and renal regulator.
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.
Takei
Yoshio
Y
Laboratory of Physiology, Department of Marine Bioscience, Ocean Research Institute, University of Tokyo, 1-15-1 Minamidai, Nakano-ku, 164-8639, Tokyo, Japan. takei@ori.u-tokyo.ac.jp
Inoue
Koji
K
Ogoshi
Maho
M
Kawahara
Tetsushi
T
Bannai
Hideo
H
Miyano
Satoru
S
D053607:Adrenomedullin; D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics* / Q000494:pharmacology*; D010802:Phylogeny; D020033:Protein Isoforms; D051381:Rats; D017208:Rats, Wistar; D017386:Sequence Homology, Amino Acid; D023721:Tetraodontiformes; D014563:Urodynamics / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000138:chemical synthesis / Q000494:pharmacology*
D018076:DNA, Complementary; D010455:Peptides; D020033:Protein Isoforms; D014662:Vasoconstrictor Agents; D053607:Adrenomedullin