This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jougasaki, M. Articles by Burnett, J. C. Search for Related Content PubMed PubMed Citation Articles by Jougasaki, M. Articles by Burnett, J. C., Jr Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Compound via MeSH Substance via MeSH

(Hypertension. 1998;32:917-922.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Autocrine Role for the Endothelin-B Receptor in the Secretion of Adrenomedullin

Michihisa Jougasaki; John A. Schirger; Robert D. Simari; ; John C. Burnett, Jr

From the Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minn.

Correspondence to Michihisa Jougasaki, MD, PhD, Cardiorenal Research Laboratory, 915 Guggenheim, Mayo Clinic and Foundation, 200 First St SW, Rochester, MN 55905. E-mail jougasaki{at}mayo.edu

Abstract—Adrenomedullin, originally discovered in human pheochromocytoma, is a vasodilating and natriuretic peptide of vascular endothelial and smooth muscle cell origin. Although endothelin-1 (ET-1) has been implicated as a vasoconstricting and growth-promoting peptide of endothelial origin, it may more importantly function as an autocrine factor and release vasodilatory substances such as nitric oxide by mechanisms linked to the endothelin-B (ET_B) receptor subtype. The present study was designed to establish that the ET_B receptor stimulates the secretion of adrenomedullin from cultured canine aortic endothelial cells. We first sought to determine the presence and production of adrenomedullin in canine aortic endothelial cells using immunohistochemistry and Northern blot analysis, which revealed that adrenomedullin immunoreactivity and adrenomedullin mRNA were present in canine aortic endothelial cells. Second, adrenomedullin was time-dependently secreted from canine aortic endothelial cells, with a secretion rate of 15.7±1.5 pg/10⁵ cells per 24 hours. Furthermore, immunohistochemistry revealed the presence of the ET_B receptor in canine aortic endothelial cells, and ET_B receptor stimulation by sarafotoxin S6c increased adrenomedullin production and secretion from canine aortic endothelial cells. Such actions were blocked with the ET_B receptor antagonist IRL-2500 but not with ET_A receptor antagonist FR-139317. These studies are the first to report an additional autocrine role of the ET_B receptor in the release of vasodilating and natriuretic peptide adrenomedullin, and they suggest another important vasoactive system regulated by the ET receptor subtype.

Key Words: endothelium • hormones • immunohistochemistry • peptides • radioimmunoassay

This article has been cited by other articles:

				Y.-F. Chan, F. Tang, and W.-S. O Adrenomedullin in the Rat Testis. II: Its Production, Actions on Inhibin Secretion, Regulation by Follicle-Stimulating Hormone, and Its Interaction with Endothelin 1 in the Sertoli Cell Biol Reprod, April 1, 2008; 78(4): 780 - 785. [Abstract] [Full Text] [PDF]

				T. Dschietzig, C. Richter, L. Asswad, G. Baumann, and K. Stangl Hypoxic Induction of Receptor Activity-Modifying Protein 2 Alters Regulation of Pulmonary Endothelin-1 by Adrenomedullin: Induction under Normoxia Versus Inhibition under Hypoxia J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 409 - 419. [Abstract] [Full Text] [PDF]

				C. P. del Villar, C. J. G. Alonso, C. A. Feldstein, L. A. Juncos, and J. C. Romero Role of Endothelin in the Pathogenesis of Hypertension Mayo Clin. Proc., January 1, 2005; 80(1): 84 - 96. [Abstract] [PDF]

				M. T. Rademaker, C. J. Charles, E. A. Espiner, M. G. Nicholls, and A. M. Richards Long-Term Adrenomedullin Administration in Experimental Heart Failure Hypertension, November 1, 2002; 40(5): 667 - 672. [Abstract] [Full Text] [PDF]

				T. Tsuruda, M. Jougasaki, G. Boerrigter, B. K. Huntley, H. H. Chen, A. B. D'Assoro, S. C. Lee, A. M. Larsen, A. Cataliotti, and J. C. Burnett Jr Cardiotrophin-1 Stimulation of Cardiac Fibroblast Growth: Roles for Glycoprotein 130/Leukemia Inhibitory Factor Receptor and the Endothelin Type A Receptor Circ. Res., February 8, 2002; 90(2): 128 - 134. [Abstract] [Full Text] [PDF]

				P. D. Upton, J. Wharton, N. Davie, M. A. Ghatei, D. M. Smith, and N. W. Morrell Differential Adrenomedullin Release and Endothelin Receptor Expression in Distinct Subpopulations of Human Airway Smooth-Muscle Cells Am. J. Respir. Cell Mol. Biol., September 1, 2001; 25(3): 316 - 325. [Abstract] [Full Text] [PDF]

				P. Kinnunen, J. Piuhola, H. Ruskoaho, and I. Szokodi AM reverses pressor response to ET-1 independently of NO in rat coronary circulation Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1178 - H1183. [Abstract] [Full Text] [PDF]

				C. B. Taner, S. R. Severson, P. J. M. Best, A. Lerman, and V. M. Miller Treatment with endothelin-receptor antagonists increases NOS activity in hypercholesterolemia J Appl Physiol, March 1, 2001; 90(3): 816 - 820. [Abstract] [Full Text] [PDF]

				M. Jougasaki and J. C Burnett Jr. Continuing insights into the heart as an endocrine organ: adrenomedullin and cardiac fibroblasts Cardiovasc Res, March 1, 2001; 49(4): 695 - 696. [Full Text] [PDF]

				T. F. Luscher and M. Barton Endothelins and Endothelin Receptor Antagonists : Therapeutic Considerations for a Novel Class of Cardiovascular Drugs Circulation, November 7, 2000; 102(19): 2434 - 2440. [Abstract] [Full Text] [PDF]

				E. Oie, L. E. Vinge, A. Yndestad, C. Sandberg, H. K. Grogaard, and H. Attramadal Induction of a Myocardial Adrenomedullin Signaling System During Ischemic Heart Failure in Rats Circulation, February 1, 2000; 101(4): 415 - 422. [Abstract] [Full Text] [PDF]

				M. Jougasaki, I. Tachibana, A. Luchner, H. Leskinen, M. M. Redfield, and J. C. Burnett Jr Augmented Cardiac Cardiotrophin-1 in Experimental Congestive Heart Failure Circulation, January 4, 2000; 101(1): 14 - 17. [Abstract] [Full Text] [PDF]

				G. G. Nussdorfer, G. P. Rossi, L. K. Malendowicz, and G. Mazzocchi Autocrine-Paracrine Endothelin System in the Physiology and Pathology of Steroid-Secreting Tissues Pharmacol. Rev., September 1, 1999; 51(3): 403 - 438. [Abstract] [Full Text] [PDF]

				E. BROCHU, S. LACASSE-M, R. LARIVIÈRE, I. KINGMA, J. H. GROSE, and M. LEBEL Differential Effects of Endothelin-1 Antagonists on Erythropoietin-Induced Hypertension in Renal Failure J. Am. Soc. Nephrol., July 1, 1999; 10(7): 1440 - 1446. [Abstract] [Full Text]

				T. Tsuruda, M. Jougasaki, G. Boerrigter, B. K. Huntley, H. H. Chen, A. B. D'Assoro, S. C. Lee, A. M. Larsen, A. Cataliotti, and J. C. Burnett Jr Cardiotrophin-1 Stimulation of Cardiac Fibroblast Growth: Roles for Glycoprotein 130/Leukemia Inhibitory Factor Receptor and the Endothelin Type A Receptor Circ. Res., February 8, 2002; 90(2): 128 - 134. [Abstract] [Full Text] [PDF]