Uroguanylin
The gut-made peptide that links salt and food in the intestine to the kidney and brain, what measuring it in people shows, and where its approved analogue fits
Uroguanylin is a 16-amino-acid peptide with two internal bridges, made mostly by cells lining the small intestine and first purified from human urine. It switches on guanylate cyclase C (GC-C), the receptor that controls salt and water secretion into the gut, and it reaches the kidney, where it promotes salt excretion. Its precursor, prouroguanylin, rises in the blood after meals and is lower in people with obesity; in mice the hormone signals fullness to the brain. Uroguanylin itself has never been given to people. The approved constipation drug plecanatide was built on its sequence and has its own entry.
No established human dose Details ↓
Recommended Dosing
No established human dose
Uroguanylin has not been given to people in any study read, so there is no dose to state. The human studies here measure the hormone or its precursor in blood, urine and gut biopsies, or apply it to human cells in the laboratory.
What is it?
Uroguanylin was found in 1994 in human urine, as a peptide that raised cyclic GMP in intestinal cells the way guanylin and the diarrhoea-causing bacterial heat-stable toxins do. It is 16 amino acids long and held in shape by two disulfide bonds. A slightly longer form, called GCAP-II, circulates in blood and ends in the same 16 residues. The body makes it as a larger precursor, prouroguanylin, mainly in the gut.
Its best-understood target is guanylate cyclase C, a receptor on the cells lining the intestine. Activating it raises cGMP, which drives chloride and water into the gut and regulates how gut cells divide and die. That is why plecanatide, a drug built on uroguanylin's sequence, relieves constipation. In mice prone to intestinal polyps, uroguanylin given by mouth halved the number of polyps, and in human colon cancer cells it triggered cell death.
Uroguanylin also travels to the kidney. In people its urinary output rose with a higher-salt diet, and in heart failure urinary uroguanylin activity was about 70 times the healthy level. In kidney disease, nephrotic syndrome and dialysis its plasma level climbs with fluid overload and failing kidney function. On human kidney collecting-duct cells it acted without GC-C, through a different pathway, which may explain how it promotes salt and water loss.
The third thread is appetite. In mice, nutrients release prouroguanylin into the blood, the hypothalamus converts it to uroguanylin, and GC-C there produces a fullness signal; high-calorie diets suppressed the hormone. In people, prouroguanylin rose more slowly after large and normal-sized meals, was lower when fasting in people with overweight or obesity, and was lower in girls with obesity. It rose after bariatric surgery in several studies. One study in mice and rats, though, found no effect of the hormone on food intake or blood sugar, so its role in human weight control is unsettled.
Uroguanylin itself has never been given to people in any study read. The approved drug plecanatide differs from it at a single amino acid and is a separate molecule with its own entry; dolcanatide and linaclotide are other GC-C agonists. Their trials are not counted here.
Mechanism of Action
Uroguanylin activates guanylate cyclase C in the gut, raising cGMP to move salt and water and steady the gut lining; in the kidney and brain it also acts through GC-C-independent routes and a gut-brain fullness signal.
Gut salt and water
Activating GC-C on intestinal cells raises cGMP and drives chloride and water into the gut (PMIDs 8141334, 7589507).
Kidney salt excretion
Urinary output rises with salt intake, and on human collecting-duct cells it acts through a GC-C-independent, phospholipase A2 route (PMIDs 9328941, 15780094).
Fullness signal
In mice, prouroguanylin released after meals is converted in the hypothalamus and activates GC-C there to reduce appetite (PMID 21865642).
Gut lining turnover
cGMP signalling slows colon cell division and triggers cell death; loss of the hormone accompanies polyps and cancer (PMID 11016642).
Published Research
These are studies of uroguanylin and its own precursor read from their PubMed abstracts: its discovery and structure, measurements in human blood, urine and gut tissue across obesity, kidney, heart and bowel disease, laboratory work on human cells, animal studies of appetite, salt and gut tumours, and a review. Trials of plecanatide, an analogue, are on that drug's entry and listed here under References only.
Discovered in human urine
Purifying urine extracts by their ability to raise cGMP in T84 intestinal cells yielded two peptides of 15 and 16 amino acids; the longer was named human uroguanylin (NDDCELCVNVACTGCL). Synthetic uroguanylin raised cGMP, competed with the bacterial heat-stable toxin for its receptor and stimulated chloride secretion.
The circulating form, GCAP-II
A 24-amino-acid peptide isolated from blood, GCAP-II, ends in the same 16 residues as urinary uroguanylin. Natural and synthetic GCAP-II activated GC-C in human colon cancer cells and drove chloride secretion in human intestinal tissue, and antibodies placed it in endocrine cells of the colon lining.
Two shapes, one active
Forming the disulfide bonds of human uroguanylin produced two topological isomers that NMR showed to interconvert in water at rates depending on pH and temperature. Only one isomer raised cGMP, which matters for measuring its activity in the body and in the dish.
Salt intake and kidney disease
A new radioimmunoassay found 24-hour urinary uroguanylin of 138 pmol on a higher-salt diet against 95 pmol on a lower-salt diet, tracking sodium, chloride, potassium and cGMP output. Plasma levels rose with serum creatinine, and the 10 kDa precursor's share grew as kidney function worsened.
Raised in nephrotic syndrome
Patients with nephrotic syndrome had higher plasma uroguanylin and lower urinary excretion than patients with other glomerular disease. Plasma levels fell in remission and rose with lower blood protein and with fluid retention.
Very high in dialysis patients
Plasma uroguanylin was about 212 fmol/mL in 76 haemodialysis patients and 245 in 10 peritoneal dialysis patients, against 5 in healthy controls. It rose with excess fluid weight and time on dialysis, and high-flux dialysis membranes lowered it.
Urinary uroguanylin in heart failure
In 53 healthy people urinary uroguanylin bioactivity peaked between 8 am and 2 pm and tended to be higher in men. In 16 patients with congestive heart failure it was about 70 times higher, and the peptide purified from their urine was the active 16-residue form.
A GC-C-independent route in the human kidney
In principal cells of human cortical collecting ducts, uroguanylin and guanylin depolarised the cells, an effect blocked by barium or a phospholipase A2 inhibitor; GC-C was not expressed there. The authors propose that the peptides close potassium channels and so reduce sodium and water reabsorption.
Lower in obesity, and lipolysis in fat cells
In 134 people, circulating prouroguanylin, unlike proguanylin, was lower in obesity in proportion to body fat, and both rose after gastric bypass. Added to human visceral fat cells in the dish, uroguanylin increased fat breakdown (lipolysis) and switched on lipolysis-related genes.
How prouroguanylin responds to meals
A high-calorie high-fat meal raised plasma prouroguanylin from 60 to 120 minutes, a medium meal only by 120 minutes, and a carbohydrate breakfast first lowered it at 30 minutes then raised it. Fasting levels were lower in people with overweight or obesity, but the after-meal response was the same.
A pilot in adolescents
In 24 adolescents aged 14 to 17 sampled fasting and after a meal, girls with obesity had lower circulating prouroguanylin than girls without, while boys showed no difference. In girls with obesity, higher inflammatory markers went with lower prouroguanylin.
Children, sex and puberty
In 117 children and adolescents, lean girls before puberty had higher prouroguanylin than lean boys, and during puberty the pattern reversed. In girls it fell with age, puberty stage, weight and BMI, while in boys it rose with BMI and waist size.
Less uroguanylin in gut biopsies of girls with obesity
In normal intestinal biopsies from 20 matched pairs of children aged 8 to 17, girls with high BMI-for-age stained less for uroguanylin and guanylin than average-weight girls, while GC-C staining was equal. Boys showed no difference.
Sex differences in Iraqi adults
In 140 adults in Baghdad, uroguanylin was lower in women than men. In women it fell with higher HbA1c and LDL cholesterol, while in men it rose with BMI, so its links to body fat and blood sugar ran in different directions by sex.
Higher after sleeve gastrectomy
In 41 patients with severe obesity and in obese rats, circulating prouroguanylin rose after sleeve gastrectomy. Lower fat preference after surgery went with higher prouroguanylin, and in rats the operation restored uroguanylin expression in taste bud cells of the tongue.
Liver fat and fibrosis
In 214 bariatric surgery patients with biopsy-proven fatty liver disease, plasma prouroguanylin and its liver expression were lower, and both rose after surgery as the liver improved. In human liver cells uroguanylin reduced fat build-up and improved mitochondrial function, and it reversed the scarring activation of hepatic stellate cells.
Duodenal cells in diarrhoea-predominant IBS
In 12 patients with diarrhoea-predominant irritable bowel syndrome, uroguanylin-containing cells were fewer in the duodenal villi and more numerous in the crypts than in 8 controls. Three weeks after faecal microbiota transplantation the crypt counts fell, and they tracked diarrhoea, bloating and pain.
A gut-to-brain fullness signal in mice
Mice lacking GC-C overate and became obese. Nutrients released prouroguanylin into the blood, and the hypothalamus cut it to uroguanylin, which activated GC-C and downstream appetite-suppressing pathways, defining a uroguanylin-GC-C endocrine axis.
High-calorie diets switch the signal off
In mice fed high-calorie diets for 14 weeks, gut uroguanylin fell and its after-meal release stopped, through endoplasmic reticulum stress driven by calories rather than obesity itself. Making the hormone in the brain restored fullness responses and countered weight gain, liver fat and glucose intolerance.
Fasting, leptin and uroguanylin in mice
Fasting lowered plasma and duodenal uroguanylin in mice and refeeding or leptin restored it; leptin-deficient mice had less and leptin treatment raised it. Mice on a high-fat diet had more uroguanylin in gut and plasma than lean mice.
No weight or glucose effect in rodents
Gastric bypass raised GUCA2A and GUCA2B gene expression in human gut endocrine cells, but giving uroguanylin, guanylin or their prohormones under the skin or into the brain of mice and rats did not change food intake, glucose tolerance or insulin release, and long-term overexpression did not alter body weight.
Fewer gut polyps in mice
Guanylin and uroguanylin messages were sharply reduced in human colon polyps and cancers while their receptor remained. Uroguanylin stopped T84 colon cells from dividing and triggered their death through cGMP, and given by mouth to polyp-prone Min mice it cut polyp numbers by about half.
The uroguanylin system and human disease
This review describes prouroguanylin as made mainly in the gut, with possible kidney production, and its products as mediating salt excretion after an oral salt load by GC-C-dependent and independent routes. It covers emerging roles in appetite and in suppressing gut tumours, and human studies hinting at roles in heart and kidney failure.
No Established Human Dose
Uroguanylin has not been given to people in any study read, so there is no dose to state. The human studies here measure the hormone or its precursor in blood, urine and gut biopsies, or apply it to human cells in the laboratory. The approved drug plecanatide is a separate molecule; its dosing belongs to its own entry and label, not to uroguanylin.
What this rests on: PMID 31697966, PMID 10720889, PMID 27108812.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Uroguanylin is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Uroguanylin has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Uroguanylin, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Uroguanylin stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Uroguanylin. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
Unknown: no cited half-life and no label or trial duration on this page says how long Uroguanylin lasts or how long it was given. Results reported in the studies are under Published Research.
Side effects, and when to stop or get help
From the Side Effects section: Activating GC-C moves salt and water into the gut; diarrhoea was the most common side effect of the analogue plecanatide in its phase III trial (PMID 28169285, an analogue, not uroguanylin); It promotes salt excretion through the kidney in the studies read, which could matter for people with fluid or electrolyte problems (PMIDs 9328941, 15780094); No safety data in people for uroguanylin itself. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Uroguanylin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“No study read gave uroguanylin to people, so no side effects of it in humans are known”).
Interactions
Unknown: a PubMed search for human interaction studies of Uroguanylin (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Uroguanylin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Uroguanylin's expected mass, 1,667.9 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a medicine anywhere in the sources read). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
No study read gave uroguanylin to people, so no side effects of it in humans are known.
Contraindications & Cautions
There is no uroguanylin product or label. These cautions follow from the evidence.
Legal Status
Uroguanylin is a research peptide; it is not approved as a medicine anywhere in the sources read. Its analogue plecanatide is FDA-approved and has its own entry.
Frequently Asked Questions
?What is uroguanylin?
A 16-amino-acid gut hormone, first found in human urine, that activates the receptor guanylate cyclase C. It regulates salt and water in the intestine, promotes salt loss through the kidney, and in mice signals fullness to the brain.
?How is it related to plecanatide?
Plecanatide, an approved constipation drug, was built on uroguanylin's sequence and differs by one amino acid. It is a separate molecule with its own entry and label.
?Does uroguanylin affect appetite in people?
Its precursor rises after meals and is lower when fasting in people with obesity, and it rises after bariatric surgery. Whether that changes appetite in people has not been tested, and one rodent study found no effect of the hormone on food intake.
?Why is it high in kidney and heart disease?
Plasma uroguanylin climbs as kidney function fails and fluid builds up, and urinary output is far higher in heart failure. Researchers read this as the body trying to shed salt, but its effect there is unproven.
?Has uroguanylin been given to people?
Not in any study read. Human research measures it; only its analogues, such as plecanatide and dolcanatide, have been given to people.
?What is its half-life?
No half-life figure was found in the sources read.
References
- [other] UniProt Q16661: GUC2B_HUMAN, guanylate cyclase activator 2B; peptide 97-112 is uroguanylin (NDDCELCVNVACTGCL) with disulfide bonds 100-108 and 103-111. Read October 28, 2026. https://www.uniprot.org/uniprotkb/Q16661/entry
- [pubmed] Kita T, et al. "Characterization of human uroguanylin: a member of the guanylin peptide family." Am J Physiol, 1994;266(2 Pt 2):F342-8. PMID: 8141334.
- [pubmed] Hess R, et al. "GCAP-II: isolation and characterization of the circulating form of human uroguanylin." FEBS Lett, 1995;374(1):34-8. PMID: 7589507.
- [pubmed] Chino N, et al. "Topological isomers of human uroguanylin: interconversion between biologically active and inactive isomers." FEBS Lett, 1998;421(1):27-31. PMID: 9462833.
- [clinical-trial] Kinoshita H, et al. "Urine and plasma levels of uroguanylin and its molecular forms in renal diseases." Kidney Int, 1997;52(4):1028-34. PMID: 9328941.
- [clinical-trial] Kinoshita H, et al. "Plasma and urine levels of uroguanylin, a new natriuretic peptide, in nephrotic syndrome." Nephron, 1999;81(2):160-4. PMID: 9933751.
- [clinical-trial] Fukae H, et al. "Plasma concentration of uroguanylin in patients on maintenance dialysis therapy." Nephron, 2000;84(3):206-10. PMID: 10720889.
- [clinical-trial] Carrithers SL, et al. "Increased urinary excretion of uroguanylin in patients with congestive heart failure." Am J Physiol Heart Circ Physiol, 2000;278(2):H538-47. PMID: 10666086.
- [pubmed] Sindić A, et al. "Guanylin and uroguanylin regulate electrolyte transport in isolated human cortical collecting ducts." Kidney Int, 2005;67(4):1420-7. PMID: 15780094.
- [clinical-trial] Rodríguez A, et al. "Guanylin and uroguanylin stimulate lipolysis in human visceral adipocytes." Int J Obes (Lond), 2016;40(9):1405-15. PMID: 27108812.
- [clinical-trial] Patterson M, et al. "Postprandial regulation of prouroguanylin in humans of a healthy weight and those who are overweight or with obesity." Peptides, 2020;123:170179. PMID: 31697966.
- [clinical-trial] Di Guglielmo MD, et al. "Pilot Study Measuring the Novel Satiety Hormone, Pro-Uroguanylin, in Adolescents With and Without Obesity." J Pediatr Gastroenterol Nutr, 2018;66(3):489-495. PMID: 29112082.
- [clinical-trial] Folgueira C, et al. "Circulating Pro-Uroguanylin Levels In Children And Their Relation To Obesity, Sex And Puberty." Sci Rep, 2018;8(1):14541. PMID: 30266914.
- [clinical-trial] Di Guglielmo MD, et al. "Immunohistochemical Staining for Uroguanylin, a Satiety Hormone, is Decreased in Intestinal Tissue Specimens From Female Adolescents With Obesity." Pediatr Dev Pathol, 2018;21(3):285-295. PMID: 28847213.
- [clinical-trial] Mohammed FA, et al. "Association of Uroguanylin, Body Mass Index, and Waist Circumference: Sex Differences and Obesity Implications among a Sample of Iraqi Adults in Baghdad City." J Pharm Bioallied Sci, 2024;16(Suppl 1):S406-S408. PMID: 38595491.
- [clinical-trial] Frühbeck G, et al. "High plasma and lingual uroguanylin as potential contributors to changes in food preference after sleeve gastrectomy." Metabolism, 2022;128:155119. PMID: 34990711.
- [clinical-trial] Fernández-Sáez EM, et al. "Uroguanylin prevents hepatic steatosis, mitochondrial dysfunction and fibrosis in obesity-associated NAFLD." Metabolism, 2023;147:155663. PMID: 37517791.
- [clinical-trial] Mazzawi T, et al. "Abnormal Uroguanylin Immunoreactive Cells Density in the Duodenum of Patients with Diarrhea-Predominant Irritable Bowel Syndrome Changes following Fecal Microbiota Transplantation." Gastroenterol Res Pract, 2020;2020:3520686. PMID: 32089675.
- [pubmed] Valentino MA, et al. "A uroguanylin-GUCY2C endocrine axis regulates feeding in mice." J Clin Invest, 2011;121(9):3578-88. PMID: 21865642.
- [pubmed] Kim GW, et al. "Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity." Nutr Diabetes, 2016;6(5):e211. PMID: 27214655.
- [pubmed] Folgueira C, et al. "Uroguanylin levels in intestine and plasma are regulated by nutritional status in a leptin-dependent manner." Eur J Nutr, 2016;55(2):529-536. PMID: 25743370.
- [pubmed] Fernandez-Cachon ML, et al. "Guanylin and uroguanylin mRNA expression is increased following Roux-en-Y gastric bypass, but guanylins do not play a significant role in body weight regulation and glycemic control." Peptides, 2018;101:32-43. PMID: 29289697.
- [pubmed] Shailubhai K, et al. "Uroguanylin treatment suppresses polyp formation in the Apc(Min/+) mouse and induces apoptosis in human colon adenocarcinoma cells via cyclic GMP." Cancer Res, 2000;60(18):5151-7. PMID: 11016642.
- [review] Rahbi H, et al. "The uroguanylin system and human disease." Clin Sci (Lond), 2012;123(12):659-68. PMID: 22877138.
- [pubmed] Miner PB Jr, et al. "A Randomized Phase III Clinical Trial of Plecanatide, a Uroguanylin Analog, in Patients With Chronic Idiopathic Constipation." Am J Gastroenterol, 2017;112(4):613-621. PMID: 28169285.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Status comes from Drugs@FDA (openFDA), the EMA medicines list and ClinicalTrials.gov, searched October 28, 2026. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.