Journal ArticleDOI
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 Aiyar,Anne M. Romanic,Calvert Louden,James J. Foley,Charles F. Sauermelch,Robert W. Coatney,Zhaohui Ao,Jyoti Disa,Stephen Dudley Holmes,Jeffrey M. Stadel,John D. Martin,Wu-Schyong Liu,George I. Glover,Shelagh Wilson,Dean E. McNulty,Catherine E. Ellis,Nabil Elshourbagy,Usman Shabon,John J. Trill,Douglas W. P. Hay,Eliot H. Ohlstein,Derk J. Bergsma,Stephen A. Douglas +26 more
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TLDR
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, the most potent mammalian vasoconstrictor identified so far.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.read more
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The Multifunctional Fish Gill: Dominant Site of Gas Exchange, Osmoregulation, Acid-Base Regulation, and Excretion of Nitrogenous Waste
TL;DR: The fish gill is a multipurpose organ that, in addition to providing for aquatic gas exchange, plays dominant roles in osmotic and ionic regulation, acid-base regulation, and excretion of nitrogenous wastes.
Journal ArticleDOI
Neuropeptides--an overview
Tomas Hökfelt,Christian Broberger,Zhi-Qing David Xu,Valeriy Sergeyev,Ruud Ubink,Margarita Diez +5 more
TL;DR: It seems that peptides may play a role particularly when the nervous system is stressed, challenged or afflicted by disease, and that peptidergic systems may, therefore, be targets for novel therapeutic strategies.
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The Concise Guide to PHARMACOLOGY 2013/14: G Protein‐Coupled Receptors
Stephen P.H. Alexander,Helen E. Benson,Elena Faccenda,Adam J. Pawson,Joanna L. Sharman,Michael Spedding,John A. Peters,Anthony J. Harmar +7 more
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Purification and characterization of rat des-Gln14-Ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor.
TL;DR: The purification of the second endogenous ligand for GHS-R from rat stomach is reported, named des-Gln14-ghrelin, whose sequence is identical to ghrelin except for one glutamine, and this is the first example of a novel mechanism that produces peptide multiplicity.
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Target validation of G-protein coupled receptors.
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References
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Journal ArticleDOI
A novel potent vasoconstrictor peptide produced by vascular endothelial cells.
Masashi Yanagisawa,Hiroki Kurihara,Hiroki Kurihara,Sadao Kimura,Yoko Tomobe,Mieko Kobayashi,Youji Mitsui,Yoshio Yazaki,Katsutoshi Goto,Tomoh Masaki +9 more
TL;DR: Cloning and sequencing of preproendothelin complementary DNA shows that mature endothelin is generated through an unusual proteolytic processing, and regional homologies to a group of neurotoxins suggest that endothelins is an endogenous modulator of voltage-dependent ion channels.
Journal ArticleDOI
A cleavage method which minimizes side reactions following Fmoc solid phase peptide synthesis.
TL;DR: Synthesis and cleavage of 10 peptides demonstrated the complementarity of Fmoc chemistry with Reagent K for efficient synthesis of complex peptides and assessed the relative effectiveness of various scavengers in suppressing side reactions.
Journal ArticleDOI
Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1.
Jon K. Chambers,Robert S. Ames,Derk J. Bergsma,Alison I. Muir,Laura R. Fitzgerald,Guillaume Hervieu,George M. Dytko,James J. Foley,John Martin,Wu-Schyong Liu,Janet Park,Catherine E. Ellis,Subinay Ganguly,Susan Konchar,Jane E. Cluderay,Ron A. Leslie,Shelagh Wilson,Henry M. Sarau +17 more
TL;DR: It is shown that the 353-amino-acid human orphan G-protein-coupled receptor SLC-1 expressed in HEK293 cells binds MCH with sub-nanomolar affinity, and is stimulated by MCH to mobilize intracellular Ca2+ and reduce forskolin-elevated cyclic AMP levels.
Journal ArticleDOI
Cloning of the cDNA encoding the urotensin II precursor in frog and human reveals intense expression of the urotensin II gene in motoneurons of the spinal cord
Yolaine Coulouarn,Isabelle Lihrmann,Sylvie Jégou,Youssef Anouar,Hervé Tostivint,Jean Claude Beauvillain,J. Michael Conlon,Howard A. Bern,Hubert Vaudry +8 more
TL;DR: The present study demonstrates that UII, which has long been regarded as a peptide exclusively produced by the urophysis of teleost fish, is actually present in the brain of amphibians and mammals.
Journal ArticleDOI
Urotensin II: a somatostatin-like peptide in the caudal neurosecretory system of fishes.
David Pearson,John E. Shively,Brian R. Clark,Irving I. Geschwind,Marylynn Barkley,Richard S. Nishioka,Howard A. Bern +6 more
TL;DR: Urotensin II, a peptide hormone from the caudal neurosecretory system of the teleost, Gillichthys mirabilis, was isolated by using classical chromatographic techniques and high-performance liquid chromatography (HPLC) to establish its structure.