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Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14.
Ames, R S; Sarau, H M; Chambers, J K; Willette, R N; Aiyar, N V; Romanic, A M; Louden, C S; Foley, J J; Sauermelch, C F; Coatney, R W; Ao, Z; Disa, J; Holmes, S D; Stadel, J M; Martin, J D; Liu, W S; Glover, G I; Wilson, S; McNulty, D E; Ellis, C E; Elshourbagy, N A; Shabon, U; Trill, J J; Hay, D W; Ohlstein, E H; Bergsma, D J; Douglas, S A.
Afiliación
  • Ames RS; Department of Molecular Biology, Smith Kline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA. bobvames1@sbphrd.com
Nature ; 401(6750): 282-6, 1999 Sep 16.
Article en En | MEDLINE | ID: mdl-10499587
Urotensin-II (U-II) is a vasoactive 'somatostatin-like' cyclic peptide which was originally isolated from fish spinal cords, and which has recently been cloned from man. Here we describe the identification of an orphan human G-protein-coupled receptor homologous to rat GPR14 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.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Urotensinas / Vasoconstrictores / Receptores de Superficie Celular / Proteínas de Unión al GTP / Receptores Acoplados a Proteínas G Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Nature Año: 1999 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Urotensinas / Vasoconstrictores / Receptores de Superficie Celular / Proteínas de Unión al GTP / Receptores Acoplados a Proteínas G Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Nature Año: 1999 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido