Urotensin II-related peptide
The short paralogue of urotensin II: the same ring, its own gene, and a human record made entirely of measurements
Urotensin II-related peptide (URP) is an eight-residue cyclic peptide found in rat brain in 2003 and made from its own gene, UTS2B. People, mice and rats all make the identical peptide, and it activates the same receptor as the longer urotensin II. Animal and cell work ties it to coronary flow, kidney and heart disease and, in zebrafish, to the shape of the spine. In people it has only been measured: raised in the plasma of patients admitted with heart failure and present in diseased arteries and valves. There is no medicine and no human dose.
No established human dose Details ↓
Recommended Dosing
No established human dose
No study read here gave URP to a person, so there is no human dose to state, not even a research one. The human evidence is measurement: levels in plasma compared between patients and controls, staining of surgically removed plaque and valve tissue, and experiments on human cells in culture.
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What is it?
Urotensin II-related peptide, usually shortened to URP, is an eight-residue peptide that people, mice and rats all make from the same short gene, UTS2B. Two of its residues are cysteines joined by a disulfide bond, so most of the molecule sits in a small ring. That ring is the part it shares with urotensin II, a longer peptide found decades earlier in fish, and the two bind the same receptor. URP has its own entry here because it is its own molecule with its own gene; the longer peptide is covered under urotensin II.
It was found in 2003 by a group trying to establish what rat urotensin II actually looks like. Their antibody kept finding something in brain extract that was not the peptide they were chasing, and when they purified and sequenced it they had URP instead. Cloning the gene showed the mature peptide is identical in rat, mouse and human, which is unusual and suggests the sequence matters. Injected into anaesthetised rats it lowered blood pressure, and it switched on the urotensin II receptor in cells carrying either the rat or the human version.
Most of what is known about what URP does comes from animals and from cells. In isolated rat hearts it widened the coronary vessels and limited the damage markers released after a period without blood flow. Rats made hypertensive, or left with a fraction of their kidney, carried more of its message in heart, aorta and kidney, and rats in heart failure carried more of it in every chamber. In cultured brain support cells it raised internal calcium and drove division. Zebrafish, which make two versions of the peptide, grow curved spines without them, which is the clearest single piece of evidence that the peptide is doing a necessary job somewhere.
Human work on URP is almost entirely measurement. It has been found in plasma, where it ran about four times higher in people admitted with sudden heart failure than in matched controls, and in tissue: removed carotid plaques, stenosed aortic valves and the lung lesions of lymphangioleiomyomatosis all carry more of it than their healthy comparisons. Human valve cells grown in a dish divided faster when it was added. One 2021 study worked out how the body frees it, naming plasma kallikrein, with factor XIa, plasmin and thrombin also able to cut it out of its precursor. None of this is a treatment study, and none of it establishes that the peptide causes any of the diseases it turns up in.
There is no URP medicine and no human dose. Nobody has given it to a person in any study read here, and the drug-development effort around this receptor has gone the other way: chemists have taken URP's sequence apart to build blockers and biased ligands, which is why so much of the literature is structure-activity work rather than clinical work. Anything sold under this name is a research chemical of unknown identity and purity, and the effects described above were measured in animals, in isolated organs and in cell culture.
Mechanism of Action
URP and urotensin II are read as distant relatives of somatostatin that converge on one receptor, called UT. What follows is drawn from receptor work in cells and from animal tissue; no step in it has been tested by giving the peptide to a person.
One receptor, shared with a longer peptide
URP binds and activates UT, the receptor first known as the orphan GPR14, in cells carrying either the human or the rat form. Its ring is the part urotensin II shares, which is also why antibodies confuse the two in blood (PMIDs 14550283, 23270674).
A fixed shape with a turn in the middle
Substituting residues one at a time cost binding and contractile activity almost everywhere except the final residue, and nuclear magnetic resonance put the peptide in one conformation with a turn across its middle three residues (PMID 15476952).
Vessel and heart effects in animals
In isolated rat hearts it widened coronary vessels and cut the release of damage markers after ischaemia, an effect a receptor blocker removed. Rats in heart failure or with hypertension carry more of its message in heart and kidney (PMIDs 17900760, 18314225, 18955095).
Cell growth in culture
Rat astrocytes and human aortic valve cells both divided faster with URP present, and in transfected cells it also raised calcium through two somatostatin receptor subtypes (PMIDs 20192922, 31679703, 18289730).
Cut out of its precursor by clotting enzymes
Screening a human plasma protein fraction identified plasma kallikrein as a main producer of the active peptide, with factor XIa, plasmin and thrombin also able to release it (PMID 34734734).
Published Research
These are studies of URP itself, read from their PubMed abstracts: the paper that isolated and named it, structure-activity work on the synthetic peptide, animal and cell experiments on heart, kidney, brain and spine, and the human studies, which measure the peptide in plasma and in surgically removed tissue. No study read gave URP to a person. Studies of urotensin II are carded on its own entry, and papers reporting only urotensin II results are listed under References.
An eight-residue peptide, named in rat brain
A Japanese group set out to pin down the rat version of urotensin II and instead came away with a shorter molecule, eight residues long, which they called URP. Its gene turned out to code for the same finished peptide in rats, mice and people. URP switched on the urotensin II receptor, and anaesthetised rats given it showed a fall in blood pressure. The authors reported its gene active in thymus, spleen, testis and spinal cord.
Which residues the receptor needs
Chemists made a series of altered URP molecules and tested each one for receptor binding and for its ability to contract a strip of rat aorta. Replacing almost any residue cost most of the activity, the exception being the last one. Mirror-image substitutions produced the series' first blockers rather than activators. Nuclear magnetic resonance put the peptide in a single folded shape with a turn across its middle three residues.
In mouse brain, alongside a reproductive hormone
Antibodies against the peptide lit up fibres in two regions at the base of the mouse brain and cell bodies in the preoptic area, and the matching message was found in the same neurons. Double staining put it in the same fibres and cell bodies as gonadotropin-releasing hormone. The authors proposed it as a hypothalamic peptide released with that hormone, a suggestion separate from its cardiovascular work.
Coronary effects differ by species and by peptide
Hearts from Chinook salmon and from rats were perfused and given the peptide or urotensin II from either species. Rat URP widened rat coronary arteries but was roughly ten times weaker at it than the rat's own urotensin II, and in salmon hearts both rat peptides narrowed the vessels instead. Inhibitors of nitric oxide and prostaglandin production blunted the widening, and the paper was the first to report any cardiac action for URP.
Protective in a heart deprived of blood
Rat hearts were removed, perfused and then starved of flow for 45 minutes. Hearts treated with URP beforehand showed wider coronary vessels and released less creatine kinase, a marker of muscle damage, once flow resumed. Blocking the urotensin receptor with palosuran cancelled both effects, which points at the receptor rather than some general action of the peptide.
Not only its own receptor
Hamster ovary cells were engineered to carry pig somatostatin receptors of either the sst2 or the sst5 type, which are relatives of the urotensin receptor. URP raised calcium inside the cells and made them divide faster through sst2. The result suggests the peptide is not strictly confined to the receptor it was discovered on, at least in a transfected cell line.
More of its message in a failing rat heart
Rats were put into heart failure by tying off a coronary artery, and the amount of URP message in their heart tissue was counted against sham-operated animals. It was two to four times higher depending on the chamber, with the largest rise in the infarcted part of the left ventricle. In heart muscle the URP message was about ten times more plentiful than urotensin II's, which is one reason the paralogue is hard to ignore in cardiac work.
Where the two genes are switched on in mice
Counting messages across mouse tissues put both the URP and the urotensin II gene mainly in brainstem and spinal motor neurons, with differences between individual nuclei. Outside the nervous system both appeared in skeletal muscle, testis, vagina, stomach and gall bladder, while only URP was detectable in seminal vesicle, heart, colon and thymus. The receptor's message was far more widespread, highest in skeletal muscle and prostate.
Raised in hypertensive and failing rat kidneys
Kidneys from spontaneously hypertensive rats and from rats with most of the kidney surgically removed were compared with normal controls. URP message was higher in the hypertensive animals from five weeks of age, and about six times higher in the remnant kidneys of the renal-failure group. Staining placed the peptide in tubules and in the walls and lining of blood vessels.
Hypertensive rat heart and aorta
Hearts and aortas from spontaneously hypertensive rats were compared with normal controls of the same age. URP message was higher in the aorta of the hypertensive animals, as was the receptor's, while endothelin-1's message fell in both heart and kidney. Staining found the peptide mainly in heart muscle cells, with less in the cells lining and surrounding vessels.
Acting on brain support cells
Cultured rat astrocytes responded to URP with a membrane voltage change, release of their own small peptides and a rise in internal calcium, and they divided more. Urotensin II did much the same but with a different time course and a different sensitivity to one blocking toxin, so the two peptides appear to work through overlapping rather than identical machinery in these cells.
In the lung lesions of a rare disease
Lungs from patients with lymphangioleiomyomatosis, in which abnormal muscle-like cells destroy lung tissue, were stained for URP, urotensin II and the receptor. All three were plentiful in the nodular lesions and overlapped with a marker used to diagnose the disease, and receptor protein was higher than in normal lung. The authors suggest a part in the overgrowth without testing whether blocking it changes anything.
Made by the same rat neurons as GnRH
Staining, message detection and electron microscopy were combined in male rat brain. The peptide turned up in fibres of the median eminence, where the brain hands hormones to the pituitary's blood supply, and in cell bodies of the medial septum and the diagonal band. Some anterior hypothalamic neurons carried both its message and gonadotropin-releasing hormone, and the two peptides shared the same nerve endings near the portal vessels.
Separating two peptides that look alike to an antibody
URP and urotensin II share the same ring, so an antibody raised against one can read the other, and the authors built an extraction step that pulls the two apart before each is measured. Applied to 20 people admitted with sudden heart failure and 20 matched controls, it put median plasma URP at roughly 8 pmol/L in the patients against about 2 pmol/L in the controls. Urotensin II was also higher in the patients, by much less.
Its binding sites match urotensin II's
Radiolabelled URP and urotensin II were used to map binding sites across the adult rat brain, the first such map for URP. The two distributions matched region for region, including unusual sites along the ventricles. Injecting either peptide into a ventricle switched on cells near the fourth ventricle that carried markers of glial rather than ependymal cells, showing the sites work.
The field's reference account
A pharmacology union review covers urotensin II and URP together: both are read as distant relatives of somatostatin, both act on one receptor called UT, and in mammals their genes are busiest in nerve cells of the brainstem and spinal cord, with further activity in heart, vessels, kidney and endocrine tissue. It catalogues the agonists and blockers built from the two sequences and notes that none has become a medicine.
Present in unstable neck-artery plaque
Eighty-eight plaques removed in carotid surgery were stained for urotensin II, URP and their shared receptor. All three showed up more strongly in plaques judged unstable than in stable ones, and the amount of staining tracked with calcification, inflammation and how narrow the artery was. The dish experiments in the same paper used urotensin II rather than URP, so they are not evidence about URP itself.
In stenosed aortic valves, and on human valve cells
Diseased and healthy human aortic valves were compared: URP, urotensin II and the receptor were all more abundant in the stenosed valves, and the amount matched the degree of calcification and scarring. Valve interstitial cells taken from healthy valves divided faster when URP was added and moved cholesterol out less efficiently. The authors read the system as a participant in valve disease rather than a bystander.
Which enzyme frees it in blood
URP and urotensin II are cut out of inactive precursor proteins, and nobody had named the protease that does it in plasma. The authors fractionated a human plasma protein preparation and screened the fractions by mass spectrometry for cutting activity. Plasma kallikrein accounted for much of it, and factor XIa, plasmin, thrombin and, more weakly, factor XIIa also released URP. This places the peptide's production inside the same cascade as clotting and inflammation.
Its gene responds to gut bacteria
Sensory neurons of the mouse nodose-petrosal ganglion, which carry signals from the gut to the brainstem, were compared between animals raised with and without a microbiome. The URP gene was active only in the animals with bacteria present, and in culture its activity rose with a short-chain fatty acid receptor agonist and with cholecystokinin. Labelled neurons touched gut cells that make cholecystokinin, placing the gene in a gut-to-brain route.
Zebrafish need it to grow a straight spine
Zebrafish carry two versions of the peptide, made by neurons that line the spinal canal. Fish lacking both grew normally at first and then developed sideways curves in the tail half of the spine during adolescence, and breaking one of the receptors produced much the same shape. The curves differed in position and direction from those of other curved-spine mutants, and the fibre running down the canal stayed intact, so the mechanism looks separate from the better-known one.
No Established Human Dose
No study read here gave URP to a person, so there is no human dose to state, not even a research one. The human evidence is measurement: levels in plasma compared between patients and controls, staining of surgically removed plaque and valve tissue, and experiments on human cells in culture. The amounts used in rats, in isolated hearts and in cell work are experimental conditions chosen for those systems, and they do not convert into anything a person could be given.
What this rests on: PMID 23270674, PMID 27375483, PMID 31679703, PMID 34734734, PMID 17900760.
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 Urotensin II-related peptide 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 Urotensin II-related peptide 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 Urotensin II-related peptide, 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 Urotensin II-related peptide stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Urotensin II-related peptide. 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 Urotensin II-related peptide 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: Every human study on this page measures the peptide in plasma or in removed tissue, or treats human cells in culture (PMIDs 23270674, 27375483, 31679703); The blood-pressure fall reported for the peptide was in anaesthetised rats (PMID 14550283); Effects on heart, kidney, brain cells and spine come from rats, isolated organs, cell culture and zebrafish (PMIDs 17900760, 18955095, 20192922, 36453722). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Urotensin II-related peptide. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“URP has not been given to people, so no human side effects are known”).
Interactions
Unknown: a PubMed search for human interaction studies of Urotensin II-related peptide (reviewed 2026-11-03) 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 Urotensin II-related peptide 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 Urotensin II-related peptide's expected mass, 1,017.2 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: Drugs@FDA (openFDA) and the EMA medicines list return no record for urotensin II-related peptide (November 3, 2026)). Sport: Not on the 2026 List.
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
URP has not been given to people, so no human side effects are known.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
URP is an endogenous research peptide; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is urotensin II-related peptide?
An eight-amino-acid peptide, made from the UTS2B gene, that activates the same receptor as urotensin II. Its sequence is the same in humans, mice and rats.
?How is it different from urotensin II?
Urotensin II is longer, 11 residues in people, and comes from a different gene. The two share the ring that the receptor recognises, which is why they act alike in many experiments and why antibodies struggle to tell them apart.
?Is there a URP drug or dose?
No. It has never been given to a person in the studies read here, there is no approved product, and no human dose exists. Most of the drug-design work on its sequence has aimed at blocking the receptor rather than activating it.
?What does the human evidence actually show?
That the peptide is present and often raised where cardiovascular disease is: in the plasma of people admitted with heart failure, in unstable carotid plaque, in narrowed aortic valves. Those are associations measured at one moment, not evidence that it causes the disease or that changing it would help.
?Why do zebrafish matter here?
Fish that cannot make their two versions of the peptide develop a curved spine as they mature. It is the clearest demonstration that the peptide is required for something, although what it means for people is unknown.
?Is it on the WADA prohibited list?
It is not named on the 2026 or 2027 lists. It is measured in blood and tissue rather than used as a drug; see the Legal table on this page.
References
- [pubmed] Sugo T, et al. "Identification of urotensin II-related peptide as the urotensin II-immunoreactive molecule in the rat brain." Biochem Biophys Res Commun, 2003;310(3):860-8. PMID: 14550283.
- [pubmed] Mori M, et al. "Urotensin II-related peptide, the endogenous ligand for the urotensin II receptor in the rat brain." Peptides, 2004;25(10):1815-8. PMID: 15476951.
- [pubmed] Chatenet D, et al. "Structure-activity relationships and structural conformation of a novel urotensin II-related peptide." Peptides, 2004;25(10):1819-30. PMID: 15476952.
- [pubmed] Egginger JG, et al. "A novel hypothalamic neuroendocrine peptide: URP (urotensin-II-related peptide)?." C R Biol, 2005;328(8):724-31. PMID: 16125650.
- [pubmed] Prosser HC, et al. "Cardiovascular effects of native and non-native urotensin II and urotensin II-related peptide on rat and salmon hearts." Peptides, 2006;27(12):3261-8. PMID: 17097764.
- [pubmed] Prosser HC, et al. "Urotensin II and urotensin II-related peptide (URP) in cardiac ischemia-reperfusion injury." Peptides, 2008;29(5):770-7. PMID: 17900760.
- [pubmed] Leprince J, et al. "Structure-activity relationships of urotensin II and URP." Peptides, 2008;29(5):658-73. PMID: 17931747.
- [pubmed] Malagon MM, et al. "Urotensin II and urotensin II-related peptide activate somatostatin receptor subtypes 2 and 5." Peptides, 2008;29(5):711-20. PMID: 18289730.
- [pubmed] Nakayama T, et al. "Increased gene expression of urotensin II-related peptide in the hearts of rats with congestive heart failure." Peptides, 2008;29(5):801-8. PMID: 18314225.
- [pubmed] Dubessy C, et al. "Characterization of urotensin II, distribution of urotensin II, urotensin II-related peptide and UT receptor mRNAs in mouse: evidence of urotensin II at the neuromuscular junction." J Neurochem, 2008;107(2):361-74. PMID: 18710417.
- [pubmed] Mori N, et al. "Increased expression of urotensin II-related peptide and its receptor in kidney with hypertension or renal failure." Peptides, 2009;30(2):400-8. PMID: 18955095.
- [pubmed] Hirose T, et al. "Increased expression of urotensin II, urotensin II-related peptide and urotensin II receptor mRNAs in the cardiovascular organs of hypertensive rats: comparison with endothelin-1." Peptides, 2009;30(6):1124-9. PMID: 19463745.
- [pubmed] Jarry M, et al. "The vasoactive peptides urotensin II and urotensin II-related peptide regulate astrocyte activity through common and distinct mechanisms: involvement in cell proliferation." Biochem J, 2010;428(1):113-24. PMID: 20192922.
- [pubmed] Kristof AS, et al. "Protein expression of urotensin II, urotensin-related peptide and their receptor in the lungs of patients with lymphangioleiomyomatosis." Peptides, 2010;31(8):1511-6. PMID: 20433884.
- [pubmed] Egginger JG, et al. "Direct evidence for the co-expression of URP and GnRH in a sub-population of rat hypothalamic neurones: anatomical and functional correlation." PLoS One, 2011;6(10):e26611. PMID: 22039515.
- [pubmed] Chatenet D, et al. "Discovery of new antagonists aimed at discriminating UII and URP-mediated biological activities: insight into UII and URP receptor activation." Br J Pharmacol, 2013;168(4):807-21. PMID: 22994258.
- [pubmed] Jani PP, et al. "The differential extraction and immunoluminometric assay of Urotensin II and Urotensin-related peptide in heart failure." Peptides, 2013;40:72-6. PMID: 23270674.
- [pubmed] Bucharles C, et al. "Concordant localization of functional urotensin II and urotensin II-related peptide binding sites in the rat brain: Atypical occurrence close to the fourth ventricle." J Comp Neurol, 2014;522(11):2634-49. PMID: 24478001.
- [pubmed] Vaudry H, et al. "International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, urotensin II-related peptide, and their receptor: from structure to function." Pharmacol Rev, 2015;67(1):214-58. PMID: 25535277.
- [pubmed] Albanese I, et al. "The Urotensin II System and Carotid Atherosclerosis: A Role in Vascular Calcification." Front Pharmacol, 2016;7:149. PMID: 27375483.
- [pubmed] Billard E, et al. "Insight into the role of urotensin II-related peptide tyrosine residue in UT activation." Biochem Pharmacol, 2017;144:100-107. PMID: 28784291.
- [pubmed] Merlino F, et al. "Functional Selectivity Revealed by N-Methylation Scanning of Human Urotensin II and Related Peptides." J Med Chem, 2019;62(3):1455-1467. PMID: 30615452.
- [pubmed] Khan K, et al. "Urotensin II, urotensin-related peptide, and their receptor in aortic valve stenosis." J Thorac Cardiovasc Surg, 2021;161(1):e1-e15. PMID: 31679703.
- [pubmed] Schuster R, et al. "Identifying Circulating Urotensin II and Urotensin II-Related Peptide-Generating Enzymes in the Human Plasma Fraction Cohn IV-4." J Proteome Res, 2021;20(12):5368-5378. PMID: 34734734.
- [pubmed] Yoshioka Y, et al. "Uts2b is a microbiota-regulated gene expressed in vagal afferent neurons connected to enteroendocrine cells producing cholecystokinin." Biochem Biophys Res Commun, 2022;608:66-72. PMID: 35390674.
- [pubmed] Bearce EA, et al. "Urotensin II-related peptides, Urp1 and Urp2, control zebrafish spine morphology." Elife, 2022;11. PMID: 36453722.
- [other] UniProt Q765I0 (UTS2B_HUMAN), urotensin-2B precursor; peptide 112-119 is the mature eight-residue peptide ACFWKYCV with a disulfide bond between residues 113 and 118. Read November 3, 2026. https://www.uniprot.org/uniprotkb/Q765I0/entry
Sources & Citations
Every study on this page was read from its PubMed record on November 3, 2026. The sequence, the disulfide bond and the precursor positions come from UniProt Q765I0; regulatory status comes from Drugs@FDA (openFDA) and the EMA medicines list, read the same day. 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.