| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Harry S. Truman Memorial Veterans' Hospital and the Departments of 2 Pharmacology, 3 Physiology, and 4 Pathology and Anatomical Sciences, School of Medicine, Missouri University, Columbia, Missouri 65212
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
HCO3, 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."
guanylate cyclase; intestine; urinary sodium excretion; intestinal natriuretic peptides; heat-stable enterotoxins of Escherichia coli
This article has been cited by other articles:
|
|
 |
|
  M. Kikuchi, S. Fujimoto, H. Fukae, H. Kinoshita, T. Kita, M. Nakazato, and T. Eto Role of Uroguanylin, a Peptide with Natriuretic Activity, in Rats with Experimental Nephrotic Syndrome J. Am. Soc. Nephrol., February 1, 2005; 16(2): 392 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. Forte Jr Uroguanylin: Physiological Role as a Natriuretic Hormone J. Am. Soc. Nephrol., February 1, 2005; 16(2): 291 - 292. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Feil, S. M. Lohmann, H. de Jonge, U. Walter, and F. Hofmann Cyclic GMP-Dependent Protein Kinases and the Cardiovascular System: Insights From Genetically Modified Mice Circ. Res., November 14, 2003; 93(10): 907 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. T. DOW and S. A. DAVIES Integrative Physiology and Functional Genomics of Epithelial Function in a Genetic Model Organism Physiol Rev, July 1, 2003; 83(3): 687 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Leipziger Control of epithelial transport via luminal P2 receptors Am J Physiol Renal Physiol, March 1, 2003; 284(3): F419 - F432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-H. Jin, H. M. Siragy, and R. M. Carey Renal Interstitial cGMP Mediates Natriuresis by Direct Tubule Mechanism Hypertension, September 1, 2001; 38(3): 309 - 316. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
