TY - JOUR
T1 - Novel fish-derived adrenomedullin in mammals
T2 - Structure and possible function
AU - Takei, Yoshio
AU - Hyodo, Susumu
AU - Katafuchi, Takeshi
AU - Minamino, Naoto
N1 - Funding Information:
The authors express their appreciation to Dr. Hiroshi Kawauchi and Dr. Kazuhiro Takahashi for giving them an opportunity to introduce their recent work on the adrenomedullin family in this volume. They also thank Dr. Ichiro Okano and Dr. Kenji Kangawa of National Cardiovascular Center Research Institute for providing them with cDNA clones of human CTR, CRLR and RAMPs, Dr. Koji Inoue, Miss Maho Ogoshi and Ms. Sanae Hasegawa of Ocean Research Institute for their help in the initial part of this study, and Dr. Hideo Bannai and Dr. Satoru Miyano of Institute of Medical Science, University of Tokyo and Dr. Kamon Shirakawa and Dr. Masashi Furusako of Pharmaceutical Research Center Discovery Research III, Mochida Pharmaceutical Co. Ltd., for their collaboration. This work was supported in part by Grant-in-Aid for Creative Basic Research (12NP0201) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and for Scientific Research (16207004) from the Japan Society for the Promotion of Science to Y. T.
PY - 2004/10
Y1 - 2004/10
N2 - Adrenomedullin (AM) has been recognized as a member of the calcitonin (CT)/CT gene-related peptide (CGRP) family. However, an independent AM family consisting of five paralogous peptides exists in teleost fish. Among them, the peptide named AM1 is an ortholog of mammalian AM as determined by the linkage analysis of orthologous genes and the presence of proAM N-terminal 20 peptide (PAMP)-like sequence in the prosegment. Since the peptides named AM2 and 3 are distinct from other members with respect to the precursor sequence, tissue distribution of the transcripts, and exon-intron organization, we searched for their mammalian orthologs from genome databases, which resulted in an identification of AM2 in human, rat, and mouse. AM2 was expressed abundantly in the submaxillary gland, kidney, and some vascular and digestive tissues of mice. AM2 injected in vivo induced potent cardiovascular and renal effects in mice. In the heart and kidney of mice, AM2 was localized in endothelial cells of the coronary vessels and in glomeruli and vasa recta, respectively. AM2 increased cAMP accumulation in cells expressing human CT receptor-like receptor (CRLR) and one of receptor activity-modifying proteins (RAMPs), but it was no more potent than CGRP and AM. AM2 was also less potent than CT in cells expressing CT receptor and RAMP. There remains a possibility that a new AM2-specific receptor or an additional RAMP that enables CRLR to be an AM2-specific receptor, exists in mammals.
AB - Adrenomedullin (AM) has been recognized as a member of the calcitonin (CT)/CT gene-related peptide (CGRP) family. However, an independent AM family consisting of five paralogous peptides exists in teleost fish. Among them, the peptide named AM1 is an ortholog of mammalian AM as determined by the linkage analysis of orthologous genes and the presence of proAM N-terminal 20 peptide (PAMP)-like sequence in the prosegment. Since the peptides named AM2 and 3 are distinct from other members with respect to the precursor sequence, tissue distribution of the transcripts, and exon-intron organization, we searched for their mammalian orthologs from genome databases, which resulted in an identification of AM2 in human, rat, and mouse. AM2 was expressed abundantly in the submaxillary gland, kidney, and some vascular and digestive tissues of mice. AM2 injected in vivo induced potent cardiovascular and renal effects in mice. In the heart and kidney of mice, AM2 was localized in endothelial cells of the coronary vessels and in glomeruli and vasa recta, respectively. AM2 increased cAMP accumulation in cells expressing human CT receptor-like receptor (CRLR) and one of receptor activity-modifying proteins (RAMPs), but it was no more potent than CGRP and AM. AM2 was also less potent than CT in cells expressing CT receptor and RAMP. There remains a possibility that a new AM2-specific receptor or an additional RAMP that enables CRLR to be an AM2-specific receptor, exists in mammals.
KW - Adrenomedullin 2
KW - Cardiovascular action
KW - Fish adrenomedullin family
KW - Immunohistochemical localization
KW - Receptor selectivity
KW - Renal action
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U2 - 10.1016/j.peptides.2004.06.026
DO - 10.1016/j.peptides.2004.06.026
M3 - Review article
C2 - 15476931
AN - SCOPUS:5144223712
SN - 0196-9781
VL - 25
SP - 1643
EP - 1656
JO - Peptides
JF - Peptides
IS - 10 SPEC. ISS.
ER -