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Guanylin peptides: renal actions mediated by cyclic GMP
- Source :
- American journal of physiology. Renal physiology. 278(2)
- Publication Year :
- 2000
-
Abstract
- The guanylin family of cGMP-regulating peptides has three subclasses of peptides containing either three intramolecular disulfides found in bacterial heat-stable enterotoxins (ST), or two disulfides observed in guanylin and uroguanylin, or a single disulfide exemplified by lymphoguanylin. These small, heat-stable peptides bind to and activate cell-surface receptors that have intrinsic guanylate cyclase (GC) activity. Two receptor GC signaling molecules have been identified that are highly expressed in the intestine (GC-C) and/or the kidney (OK-GC) and are selectively activated by the guanylin peptides. Stimulation of cGMP production in renal target cells by guanylin peptides in vivo or ex vivo elicits a long-lived diuresis, natriuresis, and kaliuresis. Activation of GC-C receptors in target cells of intestinal mucosa markedly stimulates the transepithelial secretion of Cl−and[Formula: see text], causing enhanced secretion of fluid and electrolytes into the intestinal lumen. Bacterial ST peptides act as mimics of guanylin and uroguanylin in the intestine, which provide a cellular mechanism underlying the diarrhea caused by ST-secreting strains of Escherichia coli. Uroguanylin and guanylin may participate in a novel endocrine axis linking the digestive system and kidney as a physiological mechanism that influences Na+homeostasis. Guanylin, uroguanylin, and/or lymphoguanylin may also serve within intrarenal signaling pathways controlling cGMP production in renal target cells. Thus we propose that guanylin regulatory peptides participate in a complex multifactorial biological process that evolved to regulate the urinary excretion of NaCl when dietary salt levels exceed the body's physiological requirements. This highly integrated and redundant mechanism allows the organism to maintain sodium balance by eliminating excess NaCl in the urine. Uroguanylin, in particular, may be a prototypical “intestinal natriuretic hormone.”
- Subjects :
- Receptors, Peptide
Physiology
Guanylin
Peptide
Kidney
Gastrointestinal Hormones
chemistry.chemical_compound
medicine
Animals
Humans
Intestinal Mucosa
Receptor
Natriuretic Peptides
Cyclic GMP
chemistry.chemical_classification
biology
biology.organism_classification
Enterobacteriaceae
Enzyme
medicine.anatomical_structure
chemistry
Biochemistry
Guanylate Cyclase
Signal transduction
Peptides
hormones, hormone substitutes, and hormone antagonists
Uroguanylin
Signal Transduction
Subjects
Details
- ISSN :
- 1931857X
- Volume :
- 278
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Renal physiology
- Accession number :
- edsair.doi.dedup.....9dfc0f0645f103328c72ad94580755d2