Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14

Robert S. Ames (), Henry M. Sarau, Johathan K. Chambers, Robert N. Willette, Nambi V. Aiyar, Anne M. Romanic, Calvert S. Louden, James J. Foley, Charles F. Sauermelch, Robert W. Coatney, Zhaohui Ao, Jyoti Disa, Stephen D. Holmes, Jeffrey M. Stadel, John D. Martin, Wu-Schyong Liu, George I. Glover, Shelagh Wilson, Dean E. McNulty, Catherine E. Ellis, Nabil A. Elshourbagy, Usman Shabon, John J. Trill, Douglas W. P. Hay, Eliot H. Ohlstein, Derk J. Bergsma and Stephen A. Douglas
Additional contact information
Robert S. Ames: Departments of Molecular Biology
Henry M. Sarau: Departments of Pulmonary and Cardiovascular Pharmacology,
Johathan K. Chambers: Departments of Functional Gene Analysis
Robert N. Willette: Departments of Pulmonary and Cardiovascular Pharmacology,
Nambi V. Aiyar: Departments of Pulmonary and Cardiovascular Pharmacology,
Anne M. Romanic: Departments of Pulmonary and Cardiovascular Pharmacology,
Calvert S. Louden: Departments of Pathology
James J. Foley: Departments of Pulmonary and Cardiovascular Pharmacology,
Charles F. Sauermelch: Departments of Pulmonary and Cardiovascular Pharmacology,
Robert W. Coatney: Laboratory Animal Sciences
Zhaohui Ao: Departments of Pulmonary and Cardiovascular Pharmacology,
Jyoti Disa: Departments of Pulmonary and Cardiovascular Pharmacology,
Stephen D. Holmes: Departments of Immunology
Jeffrey M. Stadel: Departments of Pulmonary and Cardiovascular Pharmacology,
John D. Martin: Protein Biochemistry and
Wu-Schyong Liu: Protein Biochemistry and
George I. Glover: Protein Biochemistry and
Shelagh Wilson: Departments of Functional Gene Analysis
Dean E. McNulty: Protein Biochemistry and
Catherine E. Ellis: Departments of Molecular Biology
Nabil A. Elshourbagy: Departments of Molecular Biology
Usman Shabon: Departments of Molecular Biology
John J. Trill: Gene Expression Sciences, Smith Kline Beecham Pharmaceuticals
Douglas W. P. Hay: Departments of Pulmonary and Cardiovascular Pharmacology,
Eliot H. Ohlstein: Departments of Pulmonary and Cardiovascular Pharmacology,
Stephen A. Douglas: Departments of Pulmonary and Cardiovascular Pharmacology,

Nature, 1999, vol. 401, issue 6750, 282-286

Abstract: Abstract Urotensin-II (U-II) is a vasoactive ‘somatostatin-like’ cyclic peptide which was originally isolated from fish spinal cords1,2, and which has recently been cloned from man3. Here we describe the identification of an orphan human G-protein-coupled receptor homologous to rat GPR14 (refs 4, 5) and expressed predominantly in cardiovascular tissue, which functions as a U-II receptor. Goby and human U-II bind to recombinant human GPR14 with high affinity, and the binding is functionally coupled to calcium mobilization. Human U-II is found within both vascular and cardiac tissue (including coronary atheroma) and effectively constricts isolated arteries from non-human primates. The potency of vasoconstriction of U-II is an order of magnitude greater than that of endothelin-1, making human U-II the most potent mammalian vasoconstrictor identified so far. In vivo, human U-II markedly increases total peripheral resistance in anaesthetized non-human primates, a response associated with profound cardiac contractile dysfunction. Furthermore, as U-II immunoreactivity is also found within central nervous system and endocrine tissues, it may have additional activities.

Date: 1999
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DOI: 10.1038/45809

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