Renal effects of uroguanylin and guanylin in vivo

Carrithers, Stephen L.; Hill, Michael J.; Johnson, Brett; Ohara, Soichi; Jackson, Brian A.; Ott, Cobern E.; Lorenz, John M.; Mann, Elizabeth A.; Giannella, Ralph A.; Forte, Leonard R.; Greenberg, Richard N.

doi:10.1590/s0100-879x1999001100003

Cited by 50 publications

(43 citation statements)

References 12 publications

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“…Effects of STa mediated via a signaling pathway independent of GC-C have not been detected so far. In the kidney UGN-and STa-induced natriuresis and kaliuresis in GC-C Ϫ/Ϫ mice is not disturbed in vivo (21). This indicates the existence of at least one additional receptor distinct from the GC-C receptor also in the kidney.…”

mentioning

confidence: 79%

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

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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.

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mentioning

confidence: 79%

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

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“…5) was unexpected, as the majority of previous studies reported a kaliuretic action of Ugn in isolated, perfused rat kidneys and in vivo mouse preparations (4,5,13,19,30,36). However, as mentioned above, these previous studies consistently included a diuresis that will have provided an indirect, flow-dependent stimulus for potassium excretion (20,43,48).…”

Section: Effects Of Ugn and Prougn On Potassium Excretionmentioning

confidence: 99%

“…GUANYLIN (GN) AND UROGUANYLIN (Ugn) are structurally related peptides that stimulate secretory activity in the intestine and inhibit sodium reabsorption by the kidneys (4,5,8,12,13,19,24,30,36,37). Both peptides are produced in the gastrointestinal tract; Ugn primarily by enterochromaffin (EC) cells in the small intestine and Gn by goblet cells in the colon (6,27,28,39,40).…”

mentioning

confidence: 99%

Natriuretic and antikaliuretic effects of uroguanylin and prouroguanylin in the rat

Moss

Riguera

Fellner

et al. 2010

American Journal of Physiology-Renal Physiology

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Moss NG, Riguera DA, Fellner RC, Cazzolla C, Goy MF. Natriuretic and antikaliuretic effects of uroguanylin and prouroguanylin in the rat. Am J Physiol Renal Physiol 299: F1433-F1442, 2010. First published September 22, 2010 doi:10.1152/ajprenal.00281.2010.-The peptide uroguanylin (Ugn) is stored and released as a propeptide (proUgn) by enterochromaffin cells in the intestine, and converted to Ugn and other metabolites in the renal tubules. Both proUgn and Ugn are natriuretic, although the response to proUgn is thought to depend on its conversion to Ugn within nephrons. To assess the efficiency of intrarenal conversion of proUgn to Ugn, we measured urinary Ugn excretion in rats following intravenous infusions of proUgn or Ugn. Infusion of 2 and 10 nmol proUgn/kg body wt increased plasma proUgn concentration from 2.2 Ϯ 0.3 to 5.6 Ϯ 1.3 pmol/ml and to 37 Ϯ 9.6 pmol/ml, respectively. No proUgn was detected in urine before, during, or after proUgn infusions. These two proUgn infusion doses resulted in total Ugn recovery in urine of 162 Ϯ 64 and 206 Ϯ 39 pmol/kg body wt (9 and 2% of the infused amount, respectively). By contrast, the same molar amounts of Ugn resulted in 1,009 Ϯ 477 and 5,352 Ϯ 2,133 pmol/kg body wt of Ugn in urine (recoveries of ϳ50%). Unexpectedly, comparisons of natriuretic dose-response curves for each peptide showed proUgn to be about five times more potent than Ugn, despite the relatively modest amount of Ugn generated from infused proUgn. In addition, both peptides were antikaliuretic at low doses, but in this case Ugn showed greater potency than proUgn. These data do not support Ugn as the primary active principle of proUgn for regulation of renal sodium excretion.

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“…However, the former was more detected and the total amount of uroguanylin bioactivity was increased as shown in Figure 2. Because uroguanylin has another cGMP-independent pathway unlike ANP (22) and downregulates the message for the Na ϩ /K ϩ ATPase ␥-subunit in mice (23), uroguanylin may be a candidate of natriuretic factor for nephrotic animals. However, ANP was previously suspected to be a causative factor for sodium retention in nephrotic syndrome.…”

Section: Discussionmentioning

confidence: 99%

Role of Uroguanylin, a Peptide with Natriuretic Activity, in Rats with Experimental Nephrotic Syndrome

Kikuchi¹,

Fujimoto²,

Fukae³

et al. 2005

Journal of the American Society of Nephrology

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Uroguanylin induces natriuresis and diuresis in vivo as well as in vitro and is found mainly in the intestine and the kidney. However, the roles of uroguanylin in nephrotic syndrome, which is associated with sodium and water retention, have not been determined. Therefore, changes in the urine and plasma concentration of immunoreactive uroguanylin (ir-uroguanylin) and its mRNA expression in the kidney and intestine were examined using rats with puromycin aminonucleoside (PAN)-induced nephrosis. Male Sprague-Dawley rats were separated into control and nephrotic groups, and then the urinary excretion of sodium, protein, and ir-uroguanylin was examined over time. The plasma levels and renal and intestinal mRNA expression of uroguanylin at the periods of sodium retention and remarkable natriuresis also were evaluated. The sequential changes of urinary ir-uroguanylin excretion in the nephrotic group were similar to those of urinary sodium excretion. When the urinary excretion of ir-uroguanylin and sodium peaked, the plasma level of ir-uroguanylin also increased compared with that of the control group. Uroguanylin mRNA expression in the kidney increased during the period of sodium retention and then decreased during the period of remarkable natriuresis. Uroguanylin mRNA expression in the small intestines of control and nephrotic rats were identical. However, in a unilateral PAN-induced proteinuria, uroguanylin expression significantly increased in the PAN-perfused kidney compared with that in the opposite kidney. Considering the natriuretic effect of uroguanylin, these results suggested that uroguanylin plays an important role as a natriuretic factor in nephrotic syndrome via both the circulation and the kidney itself. U roguanylin is a small peptide that activates transmembrane guanylate cyclase (GC) C, influences cellular function via intracellular cyclic guanosine monophosphate (cGMP) (1), and induces the urinary excretion of sodium and water in isolated perfused rat kidneys (2) and in mice in vivo (3). Uroguanylin and guanylin are major hormones in one family of cGMP agonists, whereas atriopeptins (atrial natriuretic peptide [ANP], brain natriuretic peptide, and C-type natriuretic peptide) are a separate and distinct family of peptides that act on different GC (GC-A, -B) to signal via cGMP. We reported that uroguanylin excretion into the urine is increased in humans and rats on a high-salt diet compared with those on a low-salt diet (4,5), indicating that uroguanylin functions as an intestinal natriuretic peptide. Moreover, uroguanylin levels are increased in the circulation of patients with renal disease and congestive heart failure (6,7). Forte et al. (8) suggested that uroguanylin participates in the physiologic maintenance of the sodium balance. However, how uroguanylin functions in the pathophysiologic mechanism of nephrotic syndrome, a condition associated with sodium and water retention, remains obscure. The present study examined serial changes in the urine and plasma concentration of immunoreactive urogua...

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Renal effects of uroguanylin and guanylin in vivo

Cited by 50 publications

References 12 publications

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

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

Natriuretic and antikaliuretic effects of uroguanylin and prouroguanylin in the rat

Role of Uroguanylin, a Peptide with Natriuretic Activity, in Rats with Experimental Nephrotic Syndrome

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