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Endocrine Reviews 21 (2): 138-167
Copyright © 2000 by The Endocrine Society

Adrenomedullin, a Multifunctional Regulatory Peptide1

Joy Patricia Hinson, Supriya Kapas and David Michael Smith

Department of Molecular and Cellular Biology (J.P.H.) and Clinical Sciences Research Centre (S.K.), St. Bartholomew’s and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, University of London, London E1 4NS; and Department of Metabolic Medicine (D.M.S.), Division of Investigative Sciences, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN United Kingdom

Since the discovery of adrenomedullin in 1993 several hundred papers have been published regarding the regulation of its secretion and the multiplicity of its actions. It has been shown to be an almost ubiquitous peptide, with the number of tissues and cell types synthesizing adrenomedullin far exceeding those that do not. In Section II of this paper we give a comprehensive review both of tissues and cell lines secreting adrenomedullin and of the mechanisms regulating gene expression. The data on circulating adrenomedullin, obtained with the various assays available, are also reviewed, and the disease states in which plasma adrenomedullin is elevated are listed. In Section III the pharmacology and biochemistry of adrenomedullin binding sites, both specific sites and calcitonin gene-related peptide (CGRP) receptors, are discussed. In particular, the putative adrenomedullin receptor clones and signal transduction pathways are described. In Section IV the various actions of adrenomedullin are discussed: its actions on cellular growth, the cardiovascular system, the central nervous system, and the endocrine system are all considered. Finally, in Section V, we consider some unresolved issues and propose future areas for research.




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[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. Zhou, Z. F. Ba, I. H. Chaudry, and P. Wang
Adrenomedullin binding protein-1 modulates vascular responsiveness to adrenomedullin in late sepsis
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2002; 283(3): R553 - R560.
[Abstract] [Full Text] [PDF]


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Pharmacol. Rev.Home page
D. R. Poyner, P. M. Sexton, I. Marshall, D. M. Smith, R. Quirion, W. Born, R. Muff, J. A. Fischer, and S. M. Foord
International Union of Pharmacology. XXXII. The Mammalian Calcitonin Gene-Related Peptides, Adrenomedullin, Amylin, and Calcitonin Receptors
Pharmacol. Rev., June 1, 2002; 54(2): 233 - 246.
[Abstract] [Full Text] [PDF]


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DiabetesHome page
H. Ruan, N. Hacohen, T. R. Golub, L. Van Parijs, and H. F. Lodish
Tumor Necrosis Factor-{alpha} Suppresses Adipocyte-Specific Genes and Activates Expression of Preadipocyte Genes in 3T3-L1 Adipocytes: Nuclear Factor-{kappa}B Activation by TNF-{alpha} Is Obligatory
Diabetes, May 1, 2002; 51(5): 1319 - 1336.
[Abstract] [Full Text] [PDF]


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Am. J. Pathol.Home page
L'H. Ouafik, S. Sauze, F. Boudouresque, O. Chinot, C. Delfino, F. Fina, V. Vuaroqueaux, C. Dussert, J. Palmari, H. Dufour, et al.
Neutralization of Adrenomedullin Inhibits the Growth of Human Glioblastoma Cell Lines in Vitro and Suppresses Tumor Xenograft Growth in Vivo
Am. J. Pathol., April 1, 2002; 160(4): 1279 - 1292.
[Abstract] [Full Text] [PDF]


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J. Appl. Physiol.Home page
A. T. Baumer, C. Schumann, B. Cremers, G. Itter, W. Linz, F. Jockenhovel, and M. Bohm
Gene expression of adrenomedullin in failing myocardium: comparison to atrial natriuretic peptide
J Appl Physiol, March 1, 2002; 92(3): 1058 - 1063.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
J. J. Miret, L. Rakhilina, L. Silverman, and B. Oehlen
Functional Expression of Heteromeric Calcitonin Gene-related Peptide and Adrenomedullin Receptors in Yeast
J. Biol. Chem., February 22, 2002; 277(9): 6881 - 6887.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Endocrinol. Metab.Home page
V. A. Cameron, D. J. Autelitano, J. J. Evans, L. J. Ellmers, E. A. Espiner, M. G. Nicholls, and A. M. Richards
Adrenomedullin expression in rat uterus is correlated with plasma estradiol
Am J Physiol Endocrinol Metab, January 1, 2002; 282(1): E139 - E146.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
G. S. Filippatos, N. Gangopadhyay, O. Lalude, N. Parameswaran, S. I. Said, W. Spielman, and B. D. Uhal
Regulation of apoptosis by vasoactive peptides
Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L749 - L761.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
D. J Autelitano, R. Ridings, and F. Tang
Adrenomedullin is a regulated modulator of neonatal cardiomyocyte hypertrophy in vitro
Cardiovasc Res, August 1, 2001; 51(2): 255 - 264.
[Abstract] [Full Text] [PDF]


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Mol Hum ReprodHome page
L.L. Nikitenko, N.S. Brown, D.M. Smith, I.Z. MacKenzie, R. Bicknell, and M.C.P. Rees
Differential and cell-specific expression of calcitonin receptor-like receptor and receptor activity modifying proteins in the human uterus
Mol. Hum. Reprod., July 1, 2001; 7(7): 655 - 664.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Renal Physiol.Home page
C. Wang, E. Dobrzynski, J. Chao, and L. Chao
Adrenomedullin gene delivery attenuates renal damage and cardiac hypertrophy in Goldblatt hypertensive rats
Am J Physiol Renal Physiol, June 1, 2001; 280(6): F964 - F971.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
D. Naot, K. E. Callon, A. Grey, G. J. S. Cooper, I. R. Reid, and J. Cornish
A Potential Role for Adrenomedullin as a Local Regulator of Bone Growth
Endocrinology, May 1, 2001; 142(5): 1849 - 1857.
[Abstract] [Full Text]


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IOVSHome page
T. Udono, K. Takahashi, M. Nakayama, A. Yoshinoya, K. Totsune, O. Murakami, Y. K. Durlu, M. Tamai, and S. Shibahara
Induction of Adrenomedullin by Hypoxia in Cultured Retinal Pigment Epithelial Cells
Invest. Ophthalmol. Vis. Sci., April 1, 2001; 42(5): 1080 - 1086.
[Abstract] [Full Text]


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Cancer Res.Home page
P. Rocchi, F. Boudouresque, A. J. Zamora, X. Muracciole, E. Lechevallier, P.-M. Martin, and L'H. Ouafik
Expression of Adrenomedullin and Peptide Amidation Activity in Human Prostate Cancer and in Human Prostate Cancer Cell Lines
Cancer Res., February 1, 2001; 61(3): 1196 - 1206.
[Abstract] [Full Text]


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StrokeHome page
M. Fujioka, K. Nishio, T. Sakaki, N. Minamino, and K. Kitamura
Adrenomedullin in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage
Stroke, December 1, 2000; 31 (12): 3079 - 3083.
[Full Text]


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J. Biol. Chem.Home page
A. Ladoux and C. Frelin
Coordinated Up-regulation by Hypoxia of Adrenomedullin and One of Its Putative Receptors (RDC-1) in Cells of the Rat Blood-Brain Barrier
J. Biol. Chem., December 15, 2000; 275(51): 39914 - 39919.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
R. Pio, A. Martinez, E. J. Unsworth, J. A. Kowalak, J. A. Bengoechea, P. F. Zipfel, T. H. Elsasser, and F. Cuttitta
Complement Factor H Is a Serum-binding Protein for Adrenomedullin, and the Resulting Complex Modulates the Bioactivities of Both Partners
J. Biol. Chem., April 6, 2001; 276(15): 12292 - 12300.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
K. M. Caron and O. Smithies
Extreme hydrops fetalis and cardiovascular abnormalities in mice lacking a functional Adrenomedullin gene
PNAS, January 16, 2001; 98(2): 615 - 619.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
R. D. Reidelberger, L. Kelsey, and D. Heimann
Effects of amylin-related peptides on food intake, meal patterns, and gastric emptying in rats
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2002; 282(5): R1395 - R1404.
[Abstract] [Full Text] [PDF]




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