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 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 agoinst 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.
Greenberg
R N
RN
Department of Medicine, University of Kentucky, Lexington, USA.
Hill
M
M
Crytzer
J
J
Krause
W J
WJ
Eber
S L
SL
Hamra
F K
FK
Forte
L R
LR
D000818:Animals; D000833:Animals, Suckling; D001427:Bacterial Toxins / Q000494:pharmacology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004768:Enterotoxins / Q000494:pharmacology*; D029968:Escherichia coli Proteins; D005768:Gastrointestinal Hormones; D007413:Intestinal Mucosa / Q000378:metabolism; D007419:Intestinal Secretions / Q000187:drug effects; D007422:Intestines / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D045283:Natriuretic Agents / Q000494:pharmacology*; D045265:Natriuretic Peptides; D010455:Peptides / Q000494:pharmacology*
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D005768:Gastrointestinal Hormones; D045283:Natriuretic Agents; D045265:Natriuretic Peptides; D010455:Peptides; C072685:guanylin; C084362:uroguanylin; C027538:heat-labile enterotoxin, E coli; D006152:Cyclic GMP