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

Takei, Yoshiyuki; Inoue, Koji; Ogoshi, Maho; Kawahara, Tetsushi; Bannai, Hideo; Miyano, Satoru

doi:10.1016/s0014-5793(03)01368-1

Cited by 255 publications

(230 citation statements)

References 37 publications

Supporting

Mentioning

223

Contrasting

Order By: Relevance

“…Amylin, co-secreted with insulin from pancreatic b cells, is now used for the treatment of type 2 diabetes (Cluck et al 2005). The second AM, named AM2/intermedin, was recently identified in the selected species of mammals based on the discovery of AM subfamily in teleost fish (Roh et al 2004, Takei et al 2004b. AM2 seems to be a multifunctional peptide as is AM but has more potent central actions than AM (Taylor et al 2005, Hashimoto et al 2007.…”

Section: Discussionmentioning

confidence: 99%

“…AM5 genes were sought in the genome and EST databases of various vertebrate species using BioGrepX program established by Dr Hideo Bannai of Kyushu University (see Takei et al 2004b). Phylogenetic analyses of newly identified AMs were performed using a Bayesian method in MrBayes program (version 3.1.2; Ronquist & Huelsenbeck 2003) to confirm their identity in the AM subfamily.…”

Section: Molecular Studiesmentioning

confidence: 99%

“…Comparative genomic analyses further showed that two paralogs of each group, AM1 and AM4, and AM2 and AM3, are generated at the third-round whole-genome duplication (3R) that occurred in the teleost lineage (Vandepoele et al 2004), but the counterpart of AM5 may have disappeared during teleost evolution (Ogoshi et al 2006). Since AM2/3 and AM5 should have existed when tetrapods (lobe-finned fishes) diverged from ray-finned fishes, we searched them in the genome and expressed sequence tag (EST) databases and identified AM2 and AM5 genes in mammals (Takei et al 2004b, Ogoshi et al 2006. The AM2 gene was also identified in mammals by a similar comparative approach and named intermedin (Roh et al 2004, Takei 2006.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Central and peripheral cardiovascular actions of adrenomedullin 5, a novel member of the calcitonin gene-related peptide family, in mammals

Takei¹,

Hashimoto

Inoue³

et al. 2008

Journal of Endocrinology

View full text Add to dashboard Cite

Adrenomedullin 5 (AM5) is a new member of the calcitonin gene-related peptide (CGRP) family identified in teleost fish. Although its presence was suggested in the genome database of mammals, molecular identity and biological function of AM5 have not been examined yet. In this study, we cloned a cDNA encoding AM5 in the pig and examined its cardiovascular and renal effects. Putative mature AM5 was localized in the middle of prohormone and had potential signals for intermolecular ring formation and C-terminal amidation. The AM5 gene was expressed most abundantly in the spleen and thymus. Several AM5 genes were newly identified in the database of mammals, which revealed that the AM5 gene exists in primates, carnivores, and undulates but could not be identified in rodents. In primates, nucleotide deletion occurred in the mature AM5 sequence in anthropoids (human and chimp) during transition from the rhesus monkey. Synthetic mature AM5 injected intravenously into rats induced dose-dependent decreases in arterial pressure at 0 . 1-1 nmol/kg without apparent changes in heart rate. The decrease was maximal in 1 min and AM5 was approximately half as potent as AM. AM5 did not cause significant changes in urine flow and urine Na C concentration at any dose. In contrast to the peripheral vasodepressor action, AM5 injected into the cerebral ventricle dose-dependently increased arterial pressure and heart rate at 0 . 1-1 nmol. The increase reached maximum more quickly after AM5 (5 min) than AM (15-20 min). AM5 added to the culture cells expressing calcitonin receptor-like receptor (CLR) or calcitonin receptor (CTR) together with one of the receptor activitymodifying proteins (RAMPs), the combination of which forms major receptors for the CGRP family, did not induce appreciable increases in cAMP production in any combination, although AM increased it at 10 K10 -10 K9 M when added to the CLR and RAMP2/3 combination. These data indicate that AM5 seems to act on as yet unknown receptor(s) for AM5, other than CLR/CTRCRAMP, to exert central and peripheral cardiovascular actions in mammals.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Molecular Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Central and peripheral cardiovascular actions of adrenomedullin 5, a novel member of the calcitonin gene-related peptide family, in mammals

Takei¹,

Hashimoto

Inoue³

et al. 2008

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

Section: Biochemistry Of Ammentioning

confidence: 99%

“…8,9 Human intermedin/AM-2 consists of 47 amino acid residues with an intramolecular ring structure formed by a disulfide bond and amidated tyrosine at the C terminus, showing structural homology with AM. 8,9 Intermedin/AM-2 was shown to shear the receptors with AM by cultured cells, 8 and in accord with this, it exerted vasodilator actions similar to AM ex vivo. 10 However, data on the biochemical and pharmacological features of this novel peptide are currently very limited, and further characterization, such as the tissue distribution and effects on vascular cells, is necessary to discuss its role in blood vessels.…”

Section: Biochemistry Of Ammentioning

confidence: 99%

Adrenomedullin

Kato

Tsuruda

Kita

et al. 2005

ATVB

145

View full text Add to dashboard Cite

Abstract-Adrenomedullin (AM) is a vasodilator peptide having a wide range of biological actions such as reduction of oxidative stress and inhibition of endothelial cell apoptosis. The AM gene is expressed in vascular walls, and AM was found to be secreted from cultured vascular endothelial cells, smooth muscle cells, and adventitial fibroblasts. Plasma AM levels in patients with arteriosclerotic vascular diseases are elevated in possible association with the severity of the disease. When administered over a relatively short period, AM dilates blood vessels via an endothelium-dependent or independent mechanism. Experiments in vitro have shown that AM exerts multiple actions on cultured vascular cells, which are mostly protective or inhibitory against vascular damage and progression of arteriosclerosis. Key Words: adrenomedullin Ⅲ vasodilatation Ⅲ endothelium Ⅲ smooth muscle cell Ⅲ arteriosclerosis C ardiovascular diseases secondary to arteriosclerosis of blood vessels are currently among the leading causes of death in developed countries. A number of factors, both humoral and mechanical, have been shown to modulate vascular function in humans as well as in experimental animals. 1 Blood vessel dysfunction resulting from an imbalance of those factors accelerates the process of vascular remodeling and atherosclerosis. 1 Vasoconstrictors including angiotensin II and endothelins not always but mostly act as proatherogenic factors, whereas vasodilators, either peptides or non-peptides, such as natriuretic peptides, nitric oxide (NO), and prostaglandin (PG) I 2 , have antiatherogenic properties. 1 In 1993, a new vasodilator peptide, adrenomedullin (AM), was isolated from the tissue extract of a human pheochromocytoma by monitoring cAMP levels in rat platelets. 2 Substantial levels of the AM peptide and gene expression were detected in the cardiovascular tissues including blood vessels. As listed in the Table, AM was found to exert a wide range of biological actions related to vascular functions in cultured cells, with which observations in vivo have been mostly accordant. Ever since the discovery of AM, efforts have been made to clarify the role of this bioactive peptide in blood vessels and a substantial amount of basic and clinical data has been accumulated. In this review, after summarizing the biochemical and pharmacological features of AM, we discuss its role in blood vessels, which is assumed to be protective, or inhibitory against the progression of vascular damage and remodeling. Biochemistry of AMHuman AM is a 52-aa peptide with a ring structure formed by a disulfide bond and amidated tyrosine at the C terminus ( Figure 1), both essential for binding to receptors and biological activity. 2-4 Based on sequence homology, AM is thought to belong to the calcitonin gene-related peptide (CGRP) superfamily. [2][3][4] Cloning of the cDNA encoding AM revealed the AM precursor peptide preproAM to comprise 185 amino acids, with the C terminus followed by a pair of basic amino acids, Arg-Arg, a typical processing signal (...

show abstract

Contribution of comparative fish studies to general endocrinology: structure and function of some osmoregulatory hormones

et al. 2006

Self Cite

View full text Add to dashboard Cite

Fish endocrinologists are commonly motivated to pursue their research driven by their own interests in these aquatic animals. However, the data obtained in fish studies not only satisfy their own interests but often contribute more generally to the studies of other vertebrates, including mammals. The life of fishes is characterized by the aquatic habitat, which demands many physiological adjustments distinct from the terrestrial life. Among them, body fluid regulation is of particular importance as the body fluids are exposed to media of varying salinities only across the thin respiratory epithelia of the gills. Endocrine systems play pivotal roles in the homeostatic control of body fluid balance. Judging from the habitat-dependent control mechanisms, some osmoregulatory hormones of fish should have undergone functional and molecular evolution during the ecological transition to the terrestrial life. In fact, water-regulating hormones such as vasopressin are essential for survival on the land, whereas ion-regulating hormones such as natriuretic peptides, guanylins and adrenomedullins are diversified and exhibit more critical functions in aquatic species. In this short review, we introduce some examples illustrating how comparative fish studies contribute to general endocrinology by taking advantage of such differences between fishes and tetrapods. In a functional context, fish studies often afford a deeper understanding of the essential actions of a hormone across vertebrate taxa. Using the natriuretic peptide family as an example, we suggest that more functional studies on fishes will bring similar rewards of understanding. At the molecular level, recent establishment of genome databases in fishes and mammals brings clues to the evolutionary history of hormone molecules via a comparative genomic approach. Because of the functional and molecular diversification of ion-regulating hormones in fishes, this approach sometimes leads to the discovery of new hormones in tetrapods as exemplified by adrenomedullin 2.

show abstract

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

Cited by 255 publications

References 37 publications

Central and peripheral cardiovascular actions of adrenomedullin 5, a novel member of the calcitonin gene-related peptide family, in mammals

Central and peripheral cardiovascular actions of adrenomedullin 5, a novel member of the calcitonin gene-related peptide family, in mammals

Adrenomedullin

Contribution of comparative fish studies to general endocrinology: structure and function of some osmoregulatory hormones

Contact Info

Product

Resources

About