Cellular effects of guanylin and uroguanylin.
Ingestion of a salty meal induces secretion of guanylin (GN) and uroguanylin (UGN) into the intestinal lumen, where they inhibit Na+ absorption and induce Cl-, HCO3-, and water secretion. Simultaneously, these hormones stimulate renal electrolyte excretion by inducing natriuresis, kaliuresis, and diuresis. GN and UGN therefore participate in the prevention of hypernatremia and hypervolemia after salty meals. The signaling pathway of GN and UGN in the intestine is well known. They activate enterocytes via guanylate cyclase C (GC-C), which leads to cGMP-dependent inhibition of Na+/H+ exchange and activation of the cystic fibrosis transmembrane regulator. In GC-C-deficient mice, GN and UGN still produce renal natriuresis, kaliuresis, and diuresis, suggesting different signaling pathways in the kidney compared with the intestine. Signaling pathways for GN and UGN in the kidney differ along the various nephron segments. In proximal tubule cells, a cGMP- and GC-C-dependent signaling was demonstrated for both peptides. In addition, UGN activates a pertussis toxin-sensitive G-protein-coupled receptor. A similar dual signaling pathway is also known for atrial natriuretic peptide. Recently, a cGMP-independent signaling pathway for GN and UGN was also shown in principal cells of the human and mouse cortical collecting duct. Because GN and UGN activate different signaling pathways in specific organs and even within the kidney, this review focuses on more recent findings on cellular effects and signaling mechanisms of these peptides and their pathophysiologic implications in the intestine and the kidney.
Sindić
Aleksandra
A
Universitätsklinikum Münster, Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, Domagkstrasse 3a, Münster 48149, Germany.
Schlatter
Eberhard
E
D000818:Animals; D001692:Biological Transport; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D006801:Humans; D006955:Hypernatremia / Q000517:prevention & control; D007408:Intestinal Absorption / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000502:physiology; D051379:Mice; D045265:Natriuretic Peptides / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D012982:Sodium, Dietary / Q000009:adverse effects; D014869:Water Intoxication / Q000517:prevention & control; D014883:Water-Electrolyte Imbalance / Q000378:metabolism / Q000517:prevention & control*
D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D018000:Receptors, Peptide; D012982:Sodium, Dietary; C072685:guanylin; C084362:uroguanylin