Mechanisms of actions of guanylin peptides in the kidney.
After a salty meal, stimulation of salt excretion via the kidney is a possible mechanism to prevent hypernatremia and hypervolemia. Besides the well known hormonal regulators of salt and water excretion in the distal nephron, arginine vasopressin and aldosterone, guanylin (GN) peptides produced in the intestine were proposed to be intestinal natriuretic peptides. These peptides inhibit Na+ absorption in the intestine and induce natriuresis, kaliuresis and diuresis in the kidney. The signaling pathway of GN peptides in the intestine is well known. They activate enterocytes via guanylate cyclase C (GC-C) and increase the cellular concentration of cGMP which leads to secretion of Cl-, HCO3- and water into the intestinal lumen and to inhibition of Na+ absorption. Guanylin peptides are filtered in the glomerulus, and additionally synthesized and excreted by tubular cells. They activate receptors located in the luminal membrane of the tubular cells along the nephron. In GC-C deficient mice renal effects of GN peptides are retained. In human, rat, and opossum proximal tubule cells, a cGMP-dependent signaling was demonstrated, but in addition GN peptides apparently also activate a PT-sensitive G-protein coupled receptor. A similar dual signaling pathway is also known for other natriuretic peptides like atrial natriuretic peptide. A cGMP-independent signaling pathway of GN peptides is also shown for principal cells of the human cortical collecting duct where the final hormonal regulation of electrolyte homeostasis takes place. This review will focus on the current knowledge on renal actions of GN peptides and specifically address novel GC-C- and cGMP-independent signaling mechanisms.
Sindić
Aleksandra
A
Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, Universitätsklinikum Münster, Domagkstrasse 3a, 48149 Münster, Germany.
Schlatter
Eberhard
E
D000595:Amino Acid Sequence; D000818:Animals; D005768:Gastrointestinal Hormones / Q000502:physiology*; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000502:physiology; D045265:Natriuretic Peptides / Q000502:physiology*; D010455:Peptides / Q000502:physiology; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D012982:Sodium, Dietary / Q000008:administration & dosage
D005768:Gastrointestinal Hormones; D045265:Natriuretic Peptides; D010455:Peptides; D018000:Receptors, Peptide; D012982:Sodium, Dietary; C118275:lymphoguanylin; C072685:guanylin; C084362:uroguanylin; D006162:Guanylate Cyclase; C000613655:Gucy2c protein, mouse; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled