ReviewNovel fish-derived adrenomedullin in mammals: structure and possible function
Introduction
Structural and functional evolution of hormones is an attractive research field and many hormones have been identified throughout vertebrate species from cyclostomes to mammals. These include anterior pituitary hormones [29], [72], natriuretic peptides [28], somatostatin [9], and others. Some hormones are demonstrated even in invertebrates such as gonadotropin releasing hormone (GnRH) [18], pituitary adenylate cyclase-activating peptide (PACAP)/glucagon family [69], insulin/insulin-like growth factor family [2], [7], renin–angiotensin system [62], and neurohypophysial hormones [77]. Most of these hormones were initially identified in mammals, and the search for their counterparts as peptide or cDNA resulted in their identification in non-mammalian species. As this volume emphasizes, however, there are several hormones that were initially identified in fish-specific tissues such as urophysis and corpuscles of Stannius and thought to be unique to fishes. However, most of them have been discovered later in tetrapods including mammals. A number of hormones are more abundantly expressed and stored in fishes than in mammals, which allows their identification in fishes more easily than in mammals as exemplified by C-type natriuretic peptide [57], [73]. Furthermore, a recent advancement of bioinformatic techniques to search for homologous peptides from genome databases often enables us to identify paralogous new peptides in fishes, which in turn leads to the discovery of their orthologs in mammals. In this short review, we will introduce our recent discovery of new adrenomedullin, named adrenomedullin 2, in mammals based on the identification of a new adrenomedullin family in fishes, and gain some perspective on its physiological function in mammals.
Section snippets
Members of CT/CGRP family
Adrenomedullin (AM), calcitonin (CT), CT gene-related peptide (CGRP), amylin (islet amyloid polypeptide), and recently discovered CT receptor-stimulating peptides [25], [26] constitute a family of structurally and functionally related peptides (Fig. 1). These peptides exert diverse biological actions not only as circulating hormones but also as paracrine factors in various tissues [79]. In particular, AM is expressed ubiquitously in various organs and tissues and exhibits many functions in the
Adrenomedullin family in fishes
Vertebrates have expanded their habitats from aquatic to terrestrial environments during the course of evolution. In terms of body fluid regulation, fishes seem to still retain a prototype of the vertebrate model. Therefore, analyses of the body fluid regulation in fish may contribute to a general understanding of the mechanisms throughout vertebrate species. It has been known that the endocrine system plays a pivotal role in body fluid regulation (osmoregulation) of fishes; prolactin is
Identification of adrenomedullin 2 in mammals
Encouraged by the discovery of a new AM family in fishes (Fig. 3), we pursued the possibility that a similar AM family exists throughout vertebrate species including mammals. Among the members of the AM family identified in teleost fish, AM2 and 3 are obviously classified into a group distinct from mammalian AM (AM1). To verify this hypothesis, we attempted to identify AM2 or 3 in mammals using the EST and genome databases that were open to public. For this purpose, we have developed a program
Perspective
In this short review, we have attempted to summarize our recent work on the identification of a new AM family in teleost fish [53], and on the discovery of new AM, named AM2, in mammals based on the fish sequence [76]. In addition to hormones, a comparative study may help identifying new receptors for the hormones. Consistent with the presence of more than four AM peptides in fishes, multiple CRLR-like receptors and more than three RAMP-like proteins have been cloned from the pufferfish,
Acknowledgements
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
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2016, Journal of Biological ChemistryThe novel tumor angiogenic factor, adrenomedullin-2, predicts survival in pancreatic adenocarcinoma
2015, Journal of Surgical ResearchCitation Excerpt :However, perhaps due to the effective barrier established by the complex cancer-stroma interactions seen in pancreatic cancer, many of the current therapeutic options for pancreatic cancer, including antiangiogenic agents, have had limited success in adequately treating the disease. [4]. Adrenomedullin-2 (ADM2) and/or intermedin is one of the calcitonin gene-related peptides (CGRPs), along with ADM, amylin, and others, that was recently discovered in 2004 [5,6]. It functions through forming complexes with calcitonin receptor-like receptors and receptor activity modifying proteins, and it fulfills multiple roles including, vasodilatory, hypotensive, angiogenic, and vascular remodeling actions [7].