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

Author

Listed:
  • 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,)

  • Derk J. Bergsma
  • Stephen A. Douglas

    (Departments of Pulmonary and Cardiovascular Pharmacology,)

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.

Suggested Citation

  • 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 & Zhaohu, 1999. "Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14," Nature, Nature, vol. 401(6750), pages 282-286, September.
    • Handle: RePEc:nat:nature:v:401:y:1999:i:6750:d:10.1038_45809
    DOI: 10.1038/45809
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