ArticleEndocrinology2008
Circulating prouroguanylin is processed to its active natriuretic form exclusively within the renal tubules.
Article in Endocrinology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Guanylate cyclase-C Signaling Axis as a theragnostic target in colorectal cancer: a systematic review of literature.Frontiers in oncology · 2023Pooled it
- Brain-derived uroguanylin as a regulator of postprandial brown adipose tissue activation: a potential therapeutic approach for metabolic disorders.Frontiers in pharmacology · 2025Article
- Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities.Frontiers in endocrinology · 2022Review
- Guanylyl Cyclase C Hormone Axis at the Intersection of Obesity and Colorectal Cancer.Molecular pharmacology · 2016Review
- Dietary salt regulates uroguanylin expression and signaling activity in the kidney, but not in the intestine.Physiological reports · 2016Article
- Characterization of immunological cross-reactivity between enterotoxigenic Escherichia coli heat-stable toxin and human guanylin and uroguanylin.Infection and immunity · 2014Article
- Pendrin, a novel transcriptional target of the uroguanylin system.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2013Review
- Current understanding of guanylin peptides actions.ISRN nephrology · 2013Review
- The pendrin anion exchanger gene is transcriptionally regulated by uroguanylin: a novel enterorenal link.American journal of physiology. Renal physiology · 2012Article
- A uroguanylin-GUCY2C endocrine axis regulates feeding in mice.The Journal of clinical investigation · 2011Article
- The rat kidney contains high levels of prouroguanylin (the uroguanylin precursor) but does not express GC-C (the enteric uroguanylin receptor).American journal of physiology. Renal physiology · 2011Article
- Defying the stereotype: non-canonical roles of the Peptide hormones guanylin and uroguanylin.Frontiers in endocrinology · 2011Article
- Natriuretic and antikaliuretic effects of uroguanylin and prouroguanylin in the rat.American journal of physiology. Renal physiology · 2010Article
- Activation of a novel natriuretic endocrine system in humans with heart failure.Clinical science (London, England : 1979) · 2010Article
- The natriuretic peptide uroguanylin elicits physiologic actions through 2 distinct topoisomers.Hypertension (Dallas, Tex. : 1979) · 2009Article
- Uroguanylin, an intestinal natriuretic peptide, is delivered to the kidney as an unprocessed propeptide.Endocrinology · 2008Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The intestine and kidney are linked by a mechanism that increases salt excretion in response to salt intake. The peptide uroguanylin (UGn) is thought to mediate this signaling axis. Therefore, it was surprising to find (as reported in a companion publication) that UGn is stored in the intestine and circulates in the plasma almost exclusively in the form of its biologically inactive propeptide precursor, prouroguanylin (proUGn), and, furthermore, that infused proUGn leads to natriuretic activity. Here, we investigate the fate of circulating proUGn. Kinetic studies show rapid renal clearance of radiolabeled propeptide. Radiolabel accumulates at high specific activity in kidney (relative to other organs) and urine (relative to plasma). The principal metabolites found in kidney homogenates are free cysteine and methionine. In contrast, urine contains cysteine, methionine, and three other radioactive peaks, one comigrating with authentic rat UGn15. Interestingly, proUGn is not converted to these or other metabolites in plasma, indicating that circulating proUGn is not processed before entering the kidney. Therefore, our findings suggest that proUGn is the true endocrine agent released in response to salt intake and that the response of the kidney is dependent on conversion of the propeptide to an active form after it reaches the renal tubules. Furthermore, proUGn metabolites (other than small amounts of cysteine and methionine) are not returned to the circulation from the kidney or any other organ. Thus, to respond to proUGn released from the gut, any target organ must use a local mechanism for production of active peptide.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.