Guanylin
The intestine's own version of a diarrhoea toxin: how guanylin moves salt and water, why its loss matters in colon cancer, and what measuring it shows
Guanylin is a 15-amino-acid peptide, held in shape by two disulfide bonds, that the intestine makes from a larger precursor, proguanylin. It switches on guanylate cyclase C (GC-C) on the gut lining, raising cyclic GMP and driving chloride and water into the gut: the same receptor that the E. coli heat-stable toxin hijacks to cause travellers' diarrhoea. Guanylin is lost early in colorectal tumours, and its precursor circulates in blood, where it has been measured in kidney disease, carcinoid tumours and diarrhoea. The constipation drugs linaclotide and plecanatide act on the same receptor. Guanylin itself has never been given to people.
No established human dose Details ↓
Recommended Dosing
No established human dose
Guanylin has not been given to people. Human studies measure its precursor in blood or its expression in gut and tumour tissue, or apply it to human intestinal strips and cells in the laboratory.
What is it?
Some strains of E. coli cause diarrhoea with a small heat-stable toxin that switches on a receptor in the gut lining, guanylate cyclase C. For years the receptor's own natural ligand was unknown. In 1992 a team purified a 15-amino-acid peptide from rat intestine that activated the same receptor in human colon cells and named it guanylin. Its sequence resembles the bacterial toxin, and it needs its two disulfide bonds to work. Human guanylin was cloned the same year, with its gene, GUCA2A, highly expressed in the ileum and colon.
Guanylin is made as a precursor. The human gene codes for 115 amino acids; cells secrete an inactive 94-residue proguanylin, and guanylin itself is the last 15 residues. In blood the circulating form is the large precursor, about 10 kilodaltons, not the short peptide. Synthetic work confirmed that the correct pairing of its four cysteines, 4 with 12 and 7 with 15, is the active one; the mispaired isomer folds differently.
On the gut lining, guanylin binds GC-C on the luminal surface, cyclic GMP rises, and chloride and bicarbonate flow out through the CFTR channel, taking water with them, while sodium absorption is reduced. In human intestinal tissue it increased chloride secretion more in the colon than in the jejunum. It is about a tenth as potent as the bacterial toxin in human colon cells. The gallbladder makes guanylin too and secretes it into bile, where it appears to regulate chloride secretion. Reviews describe guanylin and its relative uroguanylin as intestinal natriuretic peptides: after a salty meal they help the gut and kidney shed salt and water. In rats, a low-salt diet cut colonic guanylin by more than half.
Guanylin's second story is colorectal cancer. Its expression is strong in normal colon surface cells and absent in colorectal adenocarcinoma, and it is reduced already in precancerous adenomas in people and mice. In 281 patients, guanylin messenger RNA was 100- to 1,000-fold lower in more than 85% of tumours, and the protein was found in none of 54 tumours. Mice lacking guanylin have faster colonic cell turnover, and in mice diet-induced obesity silenced guanylin while restoring it removed diet-linked tumours. These findings led to the idea of replacing the lost signal with an oral GC-C drug such as linaclotide; a trial of linaclotide in patients with early-stage colorectal cancer is registered on ClinicalTrials.gov.
Because the precursor circulates, guanylin can be measured. Healthy adults have low levels, people with chronic kidney failure have levels about 25 times higher, implying the kidney clears it, and patients with carcinoid tumours have raised levels, while people with inflammatory bowel disease do not. In volunteers infected with toxin-producing E. coli, proguanylin fell in those who developed diarrhoea. In human fat cells guanylin stimulated fat breakdown in the laboratory. No study has given guanylin itself to a person; the drugs that act on its receptor are separate molecules with their own entries.
Mechanism of Action
Guanylin binds guanylate cyclase C on the luminal surface of the gut lining, raising cyclic GMP, which opens the CFTR chloride channel and reduces sodium absorption, so salt and water move into the gut.
Salt and water into the gut
GC-C activation raises cyclic GMP and drives chloride secretion, more in colon than jejunum in human tissue (PMIDs 7837099, 8390480).
Responds to salt
Low dietary salt cut colonic guanylin in rats; reviews tie the system to salt excretion after meals (PMIDs 8942754, 24967239).
Restrains colon cell growth
Without guanylin, colonic cyclic GMP falls and cell turnover speeds up; the hormone is lost in most colorectal tumours (PMIDs 12466132, 25304930).
Published Research
These studies were read from their PubMed abstracts on October 29, 2026: the discovery and cloning papers, studies of how guanylin acts on human gut tissue and cells, measurement studies in patients and volunteers, colorectal cancer tissue studies, mouse studies and reviews. None gave guanylin to a person.
Discovery: the gut's own ligand
A 15-amino-acid peptide purified from rat jejunum raised cyclic GMP in human colon carcinoma cells and displaced the E. coli heat-stable toxin from its receptor. It resembled the toxin, needed disulfide bonds to work, and was named guanylin.
Human guanylin cloned
A DNA copy of the human guanylin precursor's messenger RNA was isolated; its messenger RNA was abundant in ileum and colon, and human guanylin raised cyclic GMP in colon cells and increased current across rat colon.
The precursor and where it is made
Human and mouse precursors of 115 and 116 amino acids carry guanylin at their ends; cells secrete an inactive 94-residue proguanylin, which releases active guanylin when cut. Expression was restricted to the intestine.
The right disulfide pairing
Synthetic human guanylin with disulfides 4-12 and 7-15 bound its receptor and raised cyclic GMP as predicted; the isomer with the other pairing adopted a different, single shape.
The circulating form is the large precursor
Guanylin purified from human blood filtrate was a 10.3-kDa peptide, residues 22 to the end of the prohormone, and it raised cyclic GMP in colon cells.
Measured in blood; high in kidney failure
A radioimmunoassay found mean immunoreactive guanylin of 42 fmol/mL in 30 healthy people and about 1,074 fmol/mL in 22 patients with chronic kidney failure, suggesting the kidneys clear it.
Raised in carcinoid tumours
Plasma guanylin was normal in 30 patients with Crohn's disease or ulcerative colitis but raised in 17 with symptomatic carcinoid tumours, whose tissue contained guanylin, suggesting the tumours release it.
Falls with toxin-induced diarrhoea
In 21 volunteers deliberately infected with toxin-producing E. coli, plasma proguanylin fell markedly in the 10 who developed diarrhoea, a day after onset, but not in those who stayed well; prouroguanylin did not change.
Chloride secretion in human gut tissue
In strips of human intestine, guanylin and the E. coli toxin increased electrogenic chloride secretion through cyclic GMP, with larger effects in the colon than the jejunum.
A tenth as potent as the toxin
In human colon T84 cells, guanylin acting from the luminal side drove chloride secretion and a more than thousand-fold rise in cyclic GMP, at about one-tenth the potency of the bacterial toxin; binding data suggested two receptor affinities.
In the human gallbladder and bile
Guanylin and its receptor machinery were found in gallbladder epithelium and guanylin in bile, and in cultured bile-duct cancer cells it regulated chloride secretion, suggesting a bile-borne signal.
Low salt turns it down
In rats given low-, normal- or high-salt diets for a week, the low-salt diet cut colonic guanylin to 30-40% of normal, while high salt had no effect, fitting a role in shedding salt.
Absent in colorectal adenocarcinoma
In situ hybridisation found guanylin messenger RNA strongest in the distal small intestine and colon and robust in normal colon surface cells, but absent in colorectal adenocarcinoma.
Already reduced in adenomas
Guanylin expression was reduced in precancerous intestinal adenomas of both mice and people, marking early transformation, though strain levels did not predict adenoma risk in mice.
Universally lost in colorectal cancer
In tumours from 281 patients, guanylin messenger RNA was 100- to 1,000-fold lower than in nearby normal tissue in more than 85% of cases, most of all in patients under 50; the protein was in all 30 normal samples and none of 54 tumours.
Mice without guanylin
Guanylin-null mice grew and bred normally without malabsorption, but had lower colonic cyclic GMP and faster epithelial proliferation and migration in the colon.
Salt transport without guanylin
In guanylin-deficient mice, the proximal colon secreted chloride at rest and responded less to the E. coli toxin, while guanylin added to the gut surface still reduced absorption.
Obesity silences guanylin
In mice, diet-induced obesity switched off colonic guanylin through endoplasmic-reticulum stress, silencing GUCY2C and promoting tumours; forcing guanylin expression in the gut lining removed the diet-linked tumours.
Fat breakdown in human fat cells
In 134 people, intestinal GUCA2A was higher in obese people with type 2 diabetes; in cultured human omental fat cells, guanylin and uroguanylin stimulated fat breakdown.
The guanylin peptides as gut natriuretic hormones
A review describes guanylin and uroguanylin as intestinal natriuretic peptides released after salty meals: in the gut they reduce sodium absorption and drive anion and water secretion through GC-C, and they increase salt and water excretion by the kidney, partly through a second pathway.
History and kidney actions
A review places guanylin among peptides with two disulfides, between the three-disulfide bacterial toxins and one-disulfide lymphoguanylin, and describes long-lasting increases in urine flow and salt excretion in kidney studies, with synergy with ANP.
No Established Human Dose
Guanylin has not been given to people. Human studies measure its precursor in blood or its expression in gut and tumour tissue, or apply it to human intestinal strips and cells in the laboratory. Treatment-style studies used mice and rats. The drugs that act on the same receptor are separate molecules, so there is no guanylin dose.
What this rests on: PMID 8137942, PMID 25304930, PMID 7837099, PMID 26773096.
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 Guanylin 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 Guanylin 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 Guanylin, 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 Guanylin stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Guanylin. 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 Guanylin 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: Its action, salt and water secretion into the gut, is the same one that the E. coli toxin exploits to cause diarrhoea (PMID 1346555); Guanylin-null mice, the opposite situation, had faster colonic cell turnover (PMID 12466132). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Guanylin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“No one has been given guanylin, so there are no human side-effect data”).
Interactions
Unknown: a PubMed search for human interaction studies of Guanylin (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 Guanylin 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 Guanylin's expected mass, 1,458.7 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 one has been given guanylin, so there are no human side-effect data.
Contraindications & Cautions
Guanylin is a research peptide and a natural hormone, not a medicine.
Legal Status
Guanylin is an endogenous hormone studied in research. It is not a medicine.
Frequently Asked Questions
?What is guanylin?
A 15-amino-acid gut hormone with two disulfide bonds, made from proguanylin (gene GUCA2A), that activates guanylate cyclase C and moves salt and water into the intestine.
?How is it related to travellers' diarrhoea?
The heat-stable toxin of some E. coli strains mimics guanylin and over-activates the same receptor. Guanylin was found while searching for the receptor's natural ligand.
?Is guanylin a medicine?
No. It has never been given to people. Linaclotide and plecanatide are separate drugs that act on the same receptor.
?What does guanylin have to do with colon cancer?
Its expression is lost in most colorectal tumours and reduced already in adenomas. In mice, losing it speeds colon cell turnover and restoring it removed diet-linked tumours.
?Can guanylin be measured in blood?
Yes, as its circulating precursor. Levels are high in kidney failure and raised in carcinoid tumours, normal in inflammatory bowel disease, and fell during toxin-induced diarrhoea in volunteers.
?How does guanylin differ from uroguanylin?
They are related peptides acting on the same receptor; reviews describe both as intestinal natriuretic hormones. Uroguanylin has its own entry.
References
- [pubmed] Currie MG, et al. "Guanylin: an endogenous activator of intestinal guanylate cyclase." Proc Natl Acad Sci U S A, 1992;89(3):947-51. PMID: 1346555.
- [pubmed] Wiegand RC, et al. "Human guanylin: cDNA isolation, structure, and activity." FEBS Lett, 1992;311(2):150-4. PMID: 1327879.
- [pubmed] de Sauvage FJ, et al. "Precursor structure, expression, and tissue distribution of human guanylin." Proc Natl Acad Sci U S A, 1992;89(19):9089-93. PMID: 1409606.
- [pubmed] Nokihara K, et al. "Synthesis, solution structure, binding activity, and cGMP activation of human guanylin and its disulfide isomer." Regul Pept, 1997;70(2-3):111-20. PMID: 9272623.
- [pubmed] Kuhn M, et al. "The circulating bioactive form of human guanylin is a high molecular weight peptide (10.3 kDa)." FEBS Lett, 1993;318(2):205-9. PMID: 8095028.
- [pubmed] Kuhn M, et al. "Radioimmunoassay for circulating human guanylin." FEBS Lett, 1994;341(2-3):218-22. PMID: 8137942.
- [pubmed] Kuhn M, et al. "Circulating and tissue guanylin immunoreactivity in intestinal secretory diarrhoea." Eur J Clin Invest, 1995;25(12):899-905. PMID: 8719928.
- [pubmed] Brønstad I, et al. "Reduced Plasma Guanylin Levels Following Enterotoxigenic Escherichia coli-Induced Diarrhea." Microorganisms, 2023;11(8). PMID: 37630557.
- [pubmed] Kuhn M, et al. "Segmental differences in the effects of guanylin and Escherichia coli heat-stable enterotoxin on Cl- secretion in human gut." J Physiol, 1994;479 ( Pt 3)(Pt 3):433-40. PMID: 7837099.
- [pubmed] Forte LR, et al. "Guanylin stimulation of Cl- secretion in human intestinal T84 cells via cyclic guanosine monophosphate." J Clin Invest, 1993;91(6):2423-8. PMID: 8390480.
- [pubmed] Kulaksiz H, et al. "Guanylin regulates chloride secretion in the human gallbladder via the bile fluid." Gastroenterology, 2004;126(3):732-40. PMID: 14988827.
- [pubmed] Li Z, et al. "Low salt intake down-regulates the guanylin signaling pathway in rat distal colon." Gastroenterology, 1996;111(6):1714-21. PMID: 8942754.
- [pubmed] Cohen MB, et al. "Guanylin mRNA expression in human intestine and colorectal adenocarcinoma." Lab Invest, 1998;78(1):101-8. PMID: 9461126.
- [pubmed] Steinbrecher KA, et al. "Expression of guanylin is downregulated in mouse and human intestinal adenomas." Biochem Biophys Res Commun, 2000;273(1):225-30. PMID: 10873591.
- [pubmed] Wilson C, et al. "The paracrine hormone for the GUCY2C tumor suppressor, guanylin, is universally lost in colorectal cancer." Cancer Epidemiol Biomarkers Prev, 2014;23(11):2328-37. PMID: 25304930.
- [pubmed] Steinbrecher KA, et al. "Targeted inactivation of the mouse guanylin gene results in altered dynamics of colonic epithelial proliferation." Am J Pathol, 2002;161(6):2169-78. PMID: 12466132.
- [pubmed] Charney AN, et al. "Effect of secretagogues and pH on intestinal transport in guanylin-deficient mice." Biochim Biophys Acta, 2004;1671(1-3):79-86. PMID: 15026148.
- [pubmed] Lin JE, et al. "Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin-GUCY2C Paracrine Signaling Axis." Cancer Res, 2016;76(2):339-46. PMID: 26773096.
- [pubmed] Rodríguez A, et al. "Guanylin and uroguanylin stimulate lipolysis in human visceral adipocytes." Int J Obes (Lond), 2016;40(9):1405-15. PMID: 27108812.
- [pubmed] Sindic A. "Current understanding of guanylin peptides actions." ISRN Nephrol, 2013;2013:813648. PMID: 24967239.
- [pubmed] Fonteles MC, et al. "Guanylin peptide family: history, interactions with ANP, and new pharmacological perspectives." Can J Physiol Pharmacol, 2011;89(8):575-85. PMID: 21815750.
- [other] UniProt Q02747: GUC2A_HUMAN, guanylin; peptide 101-115 is guanylin (PGTCEICAYAACTGC) with disulfide bonds 104-112 and 107-115. Read October 28, 2026. https://www.uniprot.org/uniprotkb/Q02747/entry
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. The sequence and disulfides are UniProt Q02747's. Status comes from Drugs@FDA (openFDA), the EMA medicines list and ClinicalTrials.gov. Grey Peptides sells nothing and links to no vendor.
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