Effect and distribution of intravenously injected 125 I-guanylin in rat kidney examined by high-resolution light microscopic radioautography

Furuya, Sonoko; Naruse, Satoru; Ando, Eiji; Nokihara, Kiyoshi; Hayakawa, T

doi:10.1007/s004290050090

Cited by 17 publications

(12 citation statements)

References 30 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This part of the nephron could be responsible for degradation of GN produced in the CCD and, therefore, its absence in the urine. GN decreases the cell volume and increases the luminal space in a concentration-and timedependent manner which suggest secretion of water and consequently diuresis [25]. The signaling mechanism of GN peptides in the IMCD needs further investigation.…”

Section: Signaling Mechanisms Of Gn Peptides In Collecting Ductsmentioning

confidence: 99%

“…UGN is the main representative of GN peptides found in opossum urine [30] and the only one found in rat urine [14]. ProGN is degraded by chymotrypsin located in glomeruli [27] or proximal tubules [3,28] or can be endocytozed from the lumen in proximal tubules [25]. The same proteases in the tubular lumen could cut proUGN into UGN which leads to UGN activation.…”

Section: Metabolism Of Gn Peptidesmentioning

confidence: 99%

“…GN also shows effects in the latest part of the nephron, the inner medullary collecting duct (IMCD) [25]. This part of the nephron could be responsible for degradation of GN produced in the CCD and, therefore, its absence in the urine.…”

Section: Signaling Mechanisms Of Gn Peptides In Collecting Ductsmentioning

confidence: 99%

See 2 more Smart Citations

Mechanisms of actions of guanylin peptides in the kidney

Sinđić

Schlatter

2005

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

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.

show abstract

Section: Signaling Mechanisms Of Gn Peptides In Collecting Ductsmentioning

confidence: 99%

Section: Metabolism Of Gn Peptidesmentioning

confidence: 99%

See 1 more Smart Citation

Mechanisms of actions of guanylin peptides in the kidney

Sinđić

Schlatter

2005

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

show abstract

“…Although GN and UGN are both filtered in the kidney, UGN is mainly present in urine. GN is probably degraded by chymotrypsin in the glomeruli (13) or the proximal tubules (14) or removed from the tubular fluid along the proximal tubule by endocytosis (15). Another possible source of UGN found in the urine are renal tubular cells, because mRNA for UGN as well as GN are detected in the kidney and in isolated tubule fractions (16 -18).…”

mentioning

confidence: 99%

Guanylin, Uroguanylin, and Heat-stable Euterotoxin Activate Guanylate Cyclase C and/or a Pertussis Toxin-sensitive G Protein in Human Proximal Tubule Cells

Sindiće¹,

Basoglu²,

Çerçi³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

Membrane guanylate cyclase C (GC-C) is the receptor for guanylin, uroguanylin, and heat-stable enterotoxin (STa) in the intestine. GC-C-deficient mice show resistance to STa in intestine but saluretic and diuretic effects of uroguanylin and STa are not disturbed. Here we describe the cellular effects of these peptides using immortalized human kidney epithelial (IHKE-1) cells with properties of the proximal tubule, analyzed with the slow-whole-cell patch clamp technique. Uroguanylin (10 or 100 nM) either hyperpolarized or depolarized membrane voltages (V m ). Guanylin and STa (both 10 or 100 nM), as well as 8-Br-cGMP (100 M), depolarized V m . All peptide effects were absent in the presence of 1 mM Ba 2؉ . Uroguanylin and guanylin changed V m pH dependently. Pertussis toxin (1 g/ml, 24 h) inhibited hyperpolarizations caused by uroguanylin. Depolarizations caused by guanylin and uroguanylin were blocked by the tyrosine kinase inhibitor, genistein (10 M). All three peptides increased cellular cGMP. mRNA for GC-C was detected in IHKE-1 cells and in isolated human proximal tubules. In IHKE-1 cells GC-C was also detected by immunostaining. These findings suggest that GC-C is probably the receptor for guanylin and STa. For uroguanylin two distinct signaling pathways exist in IHKE-1 cells, one involves GC-C and cGMP as second messenger, the other is cGMP-independent and connected to a pertussis toxin-sensitive G protein.

show abstract

“…Reduced Na ϩ reabsorption also decreases water reabsorption in this nephron segment and thus causes diuresis. GN was shown to decrease the cell volume and increase the luminal space in a concentration-and time-dependent manner, which suggests secretion of water and consequently diuresis (68). However, the kaliuresis also caused by guanylin peptides cannot be explained from the data obtained in the CCD and may be due to effects of these peptides in other parts of the nephron, e.g., the thick ascending limb or the medullary collecting duct.…”

Section: Signaling Mechanisms Of Guanylin Peptides In the Kidneymentioning

confidence: 94%

Cellular Effects of Guanylin and Uroguanylin

Sinđić

Schlatter

2006

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

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 ؊ , HCO 3 ؊ , 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 toxinsensitive 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.

show abstract

Effect and distribution of intravenously injected 125 I-guanylin in rat kidney examined by high-resolution light microscopic radioautography

Cited by 17 publications

References 30 publications

Mechanisms of actions of guanylin peptides in the kidney

Mechanisms of actions of guanylin peptides in the kidney

Guanylin, Uroguanylin, and Heat-stable Euterotoxin Activate Guanylate Cyclase C and/or a Pertussis Toxin-sensitive G Protein in Human Proximal Tubule Cells

Cellular Effects of Guanylin and Uroguanylin

Contact Info

Product

Resources

About