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

Background: Uroguanylin and guanylin are intestinal peptides that acti vate a receptor-guanylate cyclase, which is also a receptor for Escher ichia coli heat-stable enterotoxin (STa), These peptides may have a ro le in the body's regulation of fluid and electrolytes, Methods: STa, b ioactive guanylin, and bioactive uroguanylin were evaluated for effect s 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 c GMP response in T84 cells; and 5) an in vivo renal function assay in m ice. Results: In vivo, orally administered uroguanylin and STa but not guanylin, stimulated intestinal fluid secretion, All three peptides a ctivated intestinal guanylate cyclase and had common intestinal recept ors, In vitro, after pretreatment with chymotrypsin, only uroguanylin and STa retained agonist activity, Chymostatin preserved guanylin acti vity, STa and uroguanylin induced diuresis, natriuresis, and kaliuresi s. Guanylin was less potent than uroguanylin and STa,Conclusions: The results suggest that the endogenous intestinal peptides, uroguanylin a nd guanylin, regulate water and electrolyte homeostasis both through l ocal effects on intestinal epithelia and endocrine effects on the kidn ey.