Abstract
The discovery of endogenous bioactive peptides has typically required a lengthy identification process. Computer-assisted analysis of cDNA and genomic DNA sequence information can markedly shorten the process. A bioinformatic analysis of full-length, enriched human cDNA libraries searching for previously unidentified bioactive peptides resulted in the identification and characterization of two related peptides of 28 and 20 amino acids, which we designated salusin-alpha and salusin-beta. Salusins are translated from an alternatively spliced mRNA of TOR2A, a gene encoding a protein of the torsion dystonia family. Intravenous administration of salusin-alpha or salusin-beta to rats causes rapid, profound hypotension and bradycardia. Salusins increase intracellular Ca2+, upregulate a variety of genes and induce cell mitogenesis. Salusin-beta stimulates the release of arginine-vasopressin from rat pituitary. Expression of TOR2A mRNA and its splicing into preprosalusin are ubiquitous, and immunoreactive salusin-alpha and salusin-beta are detected in many human tissues, plasma and urine, suggesting that salusins are endocrine and/or paracrine factors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / metabolism
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Adenosine Triphosphatases / pharmacology
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Algorithms
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Alternative Splicing
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Amino Acid Sequence
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Animals
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Antihypertensive Agents / pharmacology
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Calcium / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cell Cycle Proteins
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Cells, Cultured
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Cloning, Molecular
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Hemodynamics / drug effects*
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Humans
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In Vitro Techniques
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Intercellular Signaling Peptides and Proteins
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Male
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Mitogens / pharmacology*
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Molecular Chaperones*
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Molecular Sequence Data
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / drug effects
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Peptides / genetics
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Peptides / metabolism*
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Peptides / pharmacology*
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor) / genetics
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Pituitary Gland / drug effects
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Pituitary Gland / metabolism
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Rats
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Rats, Sprague-Dawley
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Sequence Homology, Amino Acid
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Signal Transduction
Substances
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Antihypertensive Agents
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Carrier Proteins
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Cell Cycle Proteins
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Intercellular Signaling Peptides and Proteins
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Mitogens
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Molecular Chaperones
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Peptides
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TOR1A protein, human
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TOR2A protein, human
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Tor1a protein, rat
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Phosphotransferases (Alcohol Group Acceptor)
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Adenosine Triphosphatases
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Calcium