| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
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.
This article has been cited by other articles:
 |
|
 |
|
  R. Morimoto, F. Satoh, O. Murakami, T. Hirose, K. Totsune, Y. Imai, Y. Arai, T. Suzuki, H. Sasano, S. Ito, et al. Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues J. Endocrinol., July 1, 2008; 198(1): 175 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Geambasu and T. L. Krukoff Adrenomedullin acts in the lateral parabrachial nucleus to increase arterial blood pressure through mechanisms mediated by glutamate and nitric oxide Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2008; 295(1): R38 - R44. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nobata, M. Ogoshi, and Y. Takei Potent cardiovascular actions of homologous adrenomedullins in eels Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2008; 294(5): R1544 - R1553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Nishida, T. Sato, M. Miyazaki, and H. Nakaya Infarct size limitation by adrenomedullin: protein kinase A but not PI3-kinase is linked to mitochondrial KCa channels Cardiovasc Res, January 15, 2008; 77(2): 398 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.W.F. van Eijndhoven, R. Aardenburg, M.E.A. Spaanderman, J.G.R. De Mey, and L.L.H. Peeters Pregnancy Enhances the Prejunctional Vasodilator Response to Adrenomedullin in Selective Regions of the Arterial Bed of Wistar Rats Reproductive Sciences, December 1, 2007; 14(8): 771 - 779. [Abstract] [PDF]
|
|
|
|
 |
|
 C. Ertmer, A. Morelli, S. Rehberg, M. Lange, C. Hucklenbruch, H. Van Aken, M. Booke, and M. Westphal Exogenous adrenomedullin prevents and reverses hypodynamic circulation and pulmonary hypertension in ovine endotoxaemia Br. J. Anaesth., December 1, 2007; 99(6): 830 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-H. Zhang, G.-R. Li, and J.-P. Bourreau The effect of adrenomedullin on the L-type calcium current in myocytes from septic shock rats: signaling pathway Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2888 - H2893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Tsujikawa, K. Yayama, T. Hayashi, H. Matsushita, T. Yamaguchi, T. Shigeno, Y. Ogitani, M. Hirayama, T. Kato, S.-i. Fukada, et al. Hypertension and dysregulated proinflammatory cytokine production in receptor activity-modifying protein 1-deficient mice PNAS, October 16, 2007; 104(42): 16702 - 16707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Christ-Crain and B. Muller Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators Eur. Respir. J., September 1, 2007; 30(3): 556 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ribatti, M. T. Conconi, and G. G. Nussdorfer Nonclassic Endogenous Novel Regulators of Angiogenesis Pharmacol. Rev., June 1, 2007; 59(2): 185 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Q. Khan, R. J. O'Brien, J. Struck, P. Quinn, N. Morgenthaler, I. Squire, J. Davies, A. Bergmann, and L. L. Ng Prognostic Value of Midregional Pro-Adrenomedullin in Patients With Acute Myocardial Infarction: The LAMP (Leicester Acute Myocardial Infarction Peptide) Study J. Am. Coll. Cardiol., April 10, 2007; 49(14): 1525 - 1532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gibbons, R. Dackor, W. Dunworth, K. Fritz-Six, and K. M. Caron Receptor Activity-Modifying Proteins: RAMPing up Adrenomedullin Signaling Mol. Endocrinol., April 1, 2007; 21(4): 783 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Fejes-Toth and A. Naray-Fejes-Toth Early Aldosterone-Regulated Genes in Cardiomyocytes: Clues to Cardiac Remodeling? Endocrinology, April 1, 2007; 148(4): 1502 - 1510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Ramachandran, T. Arumugam, R. F. Hwang, J. K. Greenson, D. M. Simeone, and C. D. Logsdon Adrenomedullin Is Expressed in Pancreatic Cancer and Stimulates Cell Proliferation and Invasion in an Autocrine Manner via the Adrenomedullin Receptor, ADMR Cancer Res., March 15, 2007; 67(6): 2666 - 2675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Caron, J. Hagaman, T. Nishikimi, H.-S. Kim, and O. Smithies Adrenomedullin gene expression differences in mice do not affect blood pressure but modulate hypertension-induced pathology in males PNAS, February 27, 2007; 104(9): 3420 - 3425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Gonzalez-Rey, A. Chorny, F. O'Valle, and M. Delgado Adrenomedullin Protects from Experimental Arthritis by Down-Regulating Inflammation and Th1 Response and Inducing Regulatory T Cells Am. J. Pathol., January 1, 2007; 170(1): 263 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J Pearson, C. Rait, M G. Nicholls, T. G Yandle, and J. J Evans Regulation of adrenomedullin release from human endothelial cells by sex steroids and angiotensin-II. J. Endocrinol., October 1, 2006; 191(1): 171 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Nikitenko, T. Cross, L. Campo, H. Turley, R. Leek, S. Manek, R. Bicknell, and M. C.P. Rees Expression of Terminally Glycosylated Calcitonin Receptor-Like Receptor in Uterine Leiomyoma: Endothelial Phenotype and Association with Microvascular Density. Clin. Cancer Res., October 1, 2006; 12(19): 5648 - 5658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Marinoni, C. Zacharopoulou, A. Di Rocco, C. Letizia, M. Moscarini, and R. Di Iorio Effect of Betamethasone In Vivo on Placental Adrenomedullin in Human Pregnancy Reproductive Sciences, September 1, 2006; 13(6): 418 - 424. [Abstract] [PDF]
|
|
|
|
|
|
N. Schwarz, D. Renshaw, S. Kapas, and J. P Hinson Adrenomedullin increases the expression of calcitonin-like receptor and receptor activity modifying protein 2 mRNA in human microvascular endothelial cells. J. Endocrinol., August 1, 2006; 190(2): 505 - 514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E Gonzalez-Rey, A Fernandez-Martin, A Chorny, and M Delgado Therapeutic effect of urocortin and adrenomedullin in a murine model of Crohn's disease Gut, June 1, 2006; 55(6): 824 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Gonzalez-Rey, A. Chorny, N. Varela, G. Robledo, and M. Delgado Urocortin and Adrenomedullin Prevent Lethal Endotoxemia by Down-Regulating the Inflammatory Response Am. J. Pathol., June 1, 2006; 168(6): 1921 - 1930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mittra and J.-P. Bourreau Gs and Gi coupling of adrenomedullin in adult rat ventricular myocytes Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1842 - H1847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Nikitenko, N. Blucher, S. B. Fox, R. Bicknell, D. M. Smith, and M. C. P. Rees Adrenomedullin and CGRP interact with endogenous calcitonin-receptor-like receptor in endothelial cells and induce its desensitisation by different mechanisms. J. Cell Sci., March 1, 2006; 119(Pt 5): 910 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Al-Ghafra, N.M. Gude, S.P. Brennecke, and R.G. King Increased adrenomedullin protein content and mRNA expression in human fetal membranes but not placental tissue in pre-eclampsia Mol. Hum. Reprod., March 1, 2006; 12(3): 181 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Morgenthaler, J. Struck, C. Alonso, and A. Bergmann Measurement of Midregional Proadrenomedullin in Plasma with an Immunoluminometric Assay Clin. Chem., October 1, 2005; 51(10): 1823 - 1829. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Bomberger, W. S. Spielman, C. S. Hall, E. J. Weinman, and N. Parameswaran Receptor Activity-modifying Protein (RAMP) Isoform-specific Regulation of Adrenomedullin Receptor Trafficking by NHERF-1 J. Biol. Chem., June 24, 2005; 280(25): 23926 - 23935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Cuesta, A. Martinez, F. Cuttitta, and E. Zudaire Identification of Adrenomedullin in Avian Type II Pneumocytes: Increased Expression after Exposure to Air Pollutants J. Histochem. Cytochem., June 1, 2005; 53(6): 773 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Hay, G. Christopoulos, A. Christopoulos, D. R. Poyner, and P. M. Sexton Pharmacological Discrimination of Calcitonin Receptor: Receptor Activity-Modifying Protein Complexes Mol. Pharmacol., May 1, 2005; 67(5): 1655 - 1665. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Boussery, C. Delaey, and J. Van de Voorde The Vasorelaxing Effect of CGRP and Natriuretic Peptides in Isolated Bovine Retinal Arteries Invest. Ophthalmol. Vis. Sci., April 1, 2005; 46(4): 1420 - 1427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Bomberger, N. Parameswaran, C. S. Hall, N. Aiyar, and W. S. Spielman Novel Function for Receptor Activity-modifying Proteins (RAMPs) in Post-endocytic Receptor Trafficking J. Biol. Chem., March 11, 2005; 280(10): 9297 - 9307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Westphal, M. Booke, and A.T. Dinh-Xuan Adrenomedullin: a smart road from pheochromocytoma to treatment of pulmonary hypertension Eur. Respir. J., October 1, 2004; 24(4): 518 - 520. [Full Text] [PDF]
|
|
|
|
|
|
N. Ozawa, M. Shichiri, N. Fukai, T. Yoshimoto, and Y. Hirata Regulation of Adrenomedullin Gene Transcription and Degradation by the c-myc Gene Endocrinology, September 1, 2004; 145(9): 4244 - 4250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Brain and A. D. Grant Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin Physiol Rev, July 1, 2004; 84(3): 903 - 934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Luodonpaa, H. Leskinen, M. Ilves, O. Vuolteenaho, and H. Ruskoaho Adrenomedullin modulates hemodynamic and cardiac effects of angiotensin II in conscious rats Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2004; 286(6): R1085 - R1092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. W. Olson, L. E. Deal, and M. Piesman Epinephrine-Secreting Pheochromocytoma Presenting with Cardiogenic Shock and Profound Hypocalcemia Ann Intern Med, May 18, 2004; 140(10): 849 - 851. [Full Text] [PDF]
|
|
|
|
|
|
W. Huang, L. Wang, M. Yuan, J. Ma, and Y. Hui Adrenomedullin Affects Two Signal Transduction Pathways and the Migration in Retinal Pigment Epithelial Cells Invest. Ophthalmol. Vis. Sci., May 1, 2004; 45(5): 1507 - 1513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Niu, T. Shindo, H. Iwata, S. Iimuro, N. Takeda, Y. Zhang, A. Ebihara, Y. Suematsu, K. Kangawa, Y. Hirata, et al. Protective Effects of Endogenous Adrenomedullin on Cardiac Hypertrophy, Fibrosis, and Renal Damage Circulation, April 13, 2004; 109(14): 1789 - 1794. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kapas, K. Pahal, A.T. Cruchley, E. Hagi-Pavli, and J.P. Hinson Expression of Adrenomedullin and its Receptors in Human Salivary Tissue J. Dent. Res., April 1, 2004; 83(4): 333 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Balasch, M. Guimera, O. Martinez-Pasarell, J. Ros, J. A. Vanrell, and W. Jimenez Adrenomedullin and vascular endothelial growth factor production by follicular fluid macrophages and granulosa cells Hum. Reprod., April 1, 2004; 19(4): 808 - 814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. I. Caron, L. R. James, H.-S. Kim, J. Knowles, R. Uhlir, L. Mao, J. R. Hagaman, W. Cascio, H. Rockman, and O. Smithies Cardiac hypertrophy and sudden death in mice with a genetically clamped renin transgene PNAS, March 2, 2004; 101(9): 3106 - 3111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Boussery, C. Delaey, and J. Van de Voorde Influence of Adrenomedullin on Tone of Isolated Bovine Retinal Arteries Invest. Ophthalmol. Vis. Sci., February 1, 2004; 45(2): 552 - 559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Hagi-Pavli, P. M. Farthing, and S. Kapas Stimulation of adhesion molecule expression in human endothelial cells (HUVEC) by adrenomedullin and corticotrophin Am J Physiol Cell Physiol, February 1, 2004; 286(2): C239 - C246. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. M. Kravtsov, I. S. S. Hwang, and F. Tang The Inhibitory Effect of Adrenomedullin in the Rat Ileum: Cross-Talk with {beta}3-Adrenoceptor in the Serotonin-Induced Muscle Contraction J. Pharmacol. Exp. Ther., January 1, 2004; 308(1): 241 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Li, J. Dakour, S. Kaufman, L. J. Guilbert, B. Winkler-Lowen, and D. W. Morrish Adrenomedullin Is Decreased in Preeclampsia Because of Failed Response to Epidermal Growth Factor and Impaired Syncytialization Hypertension, November 1, 2003; 42(5): 895 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. S. Dettmann, I. Vysniauskiene, R. Wu, J. Flammer, and I. O. Haefliger Adrenomedullin-Induced Endothelium-Dependent Relaxation in Porcine Ciliary Arteries Invest. Ophthalmol. Vis. Sci., September 1, 2003; 44(9): 3961 - 3966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Yoshikawa, F. Kawahara, N. Okano, H. Hiraoka, Y. Kadoi, N. Fujita, T. Morita, and F. Goto Increased Plasma Concentrations of the Mature Form of Adrenomedullin During Cardiac Surgery and Hepatosplanchnic Hypoperfusion Anesth. Analg., September 1, 2003; 97(3): 663 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nakatsuka, T. Habara, S. Noguchi, H. Konishi, and T. Kudo Increased Plasma Adrenomedullin in Women With Recurrent Pregnancy Loss Obstet. Gynecol., August 1, 2003; 102(2): 319 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Allaker and S. Kapas Adrenomedullin Expression by Gastric Epithelial Cells in Response to Infection Clin. Vaccine Immunol., July 1, 2003; 10(4): 546 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Fukai, M. Shichiri, N. Ozawa, M. Matsushita, and Y. Hirata Coexpression of Calcitonin Receptor-Like Receptor and Receptor Activity-Modifying Protein 2 or 3 Mediates the Antimigratory Effect of Adrenomedullin Endocrinology, February 1, 2003; 144(2): 447 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Hasbak, O. S. Opgaard, K. Eskesen, S. Schifter, H. Arendrup, J. Longmore, and L. Edvinsson Investigation of CGRP Receptors and Peptide Pharmacology in Human Coronary Arteries. Characterization with a Nonpeptide Antagonist J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 326 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Marutsuka, K. Hatakeyama, A. Yamashita, Y. Sato, A. Sumiyoshi, and Y. Asada Adrenomedullin augments the release and production of tissue factor pathway inhibitor in human aortic endothelial cells Cardiovasc Res, January 1, 2003; 57(1): 232 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hippenstiel, M. Witzenrath, B. Schmeck, A. Hocke, M. Krisp, M. Krull, J. Seybold, W. Seeger, W. Rascher, H. Schutte, et al. Adrenomedullin Reduces Endothelial Hyperpermeability Circ. Res., October 4, 2002; 91(7): 618 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Neri, S. Bova, L. K. Malendowicz, G. Mazzocchi, and G. G. Nussdorfer Simulated microgravity impairs aldosterone secretion in rats: possible involvement of adrenomedullin Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2002; 283(4): R832 - R836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tokudome, T. Horio, F. Yoshihara, S.-i. Suga, Y. Kawano, M. Kohno, and K. Kangawa Adrenomedullin Inhibits Doxorubicin-Induced Cultured Rat Cardiac Myocyte Apoptosis via a cAMP-Dependent Mechanism Endocrinology, September 1, 2002; 143(9): 3515 - 3521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
