Comparison of Effects of Uroguanylin, Guanylin, and Escherichia coli Heat-Stable Enterotoxin STa in Mouse Intestine and Kidney: Evidence that Uroguanylin is an Intestinal Natriuretic Hormone

Richard N. Greenberg, Michael Hill, Jessica Crytzer, William J. Krause, Sammy L. Eber, F. Kent Hamra, Leonard R. Forte

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Background: Uroguanylin and guanylin are intestinal peptides that activate a receptor-guanylate cyclase, which is also a receptor for Escherichia coli heat-stable enterotoxin (STa). These peptides may have a role in the body's regulation of fluid and electrolytes. Methods: STa, bioactive guanylin, and bioactive uroguanylin were evaluated for effects in: 1) the suckling mouse intestinal fluid secretion assay; 2) an in vitro suckling mouse intestinal loop assay; 3) an intestinal receptor autoradiography assay; 4) a control or agonist-stimulated assay for cGMP response in T84 cells; and 5) an in vivo renal function assay in mice. Results: In vivo, orally administered uroguanylin and STa but not guanylin, stimulated intestinal fluid secretion. All three peptides activated intestinal guanylate cyclase and had common intestinal receptors. In vitro, after pretreatment with chymotrypsin, only uroguanylin and STa retained agonist activity. Chymostatin preserved guanylin activity. STa and uroguanylin induced diuresis, natriuresis, and kaliuresis. Guanylin was less potent than uroguanylin and STa. Conclusions: The results suggest that the endogenous intestinal peptides, uroguanylin and guanylin, regulate water and electrolyte homeostasis both through local effects on intestinal epithelia and endocrine effects on the kidney.

Original languageEnglish (US)
Pages (from-to)276-283
Number of pages8
JournalJournal of Investigative Medicine
Volume45
Issue number5
StatePublished - Jun 1997

Keywords

  • Chymotrypsin
  • Cyclic GMP
  • Diuresis
  • Guanylate cyclase
  • Kaliuresis
  • Natriuresis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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