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- and salusin-. Salusins are translated from an alternatively spliced mRNA of TOR2A, a gene encoding a protein of the torsion dystonia family. Intravenous administration of salusin- or salusin- to rats causes rapid, profound hypotension and bradycardia. Salusins increase intracellular Ca²⁺, upregulate a variety of genes and induce cell mitogenesis. Salusin- stimulates the release of arginine-vasopressin from rat pituitary. Expression of TOR2A mRNA and its splicing into preprosalusin are ubiquitous, and immunoreactive salusin- and salusin- are detected in many human tissues, plasma and urine, suggesting that salusins are endocrine and/or paracrine factors.