Storage Stability
Urotensin I (UI) is a 41-amino-acid neuropeptide first isolated from the urophysis (caudal neurosecretory system) of teleost fish. It belongs to the CRF/sauvagine/urotensin-I family and acts as a potent agonist at CRF2 receptors, producing cardiovascular, osmoregulatory, and stress-axis effects distinct from mammalian CRH.
Mechanism of Action
- High-affinity CRF2 receptor agonist; selectivity profile: CRF2 > CRF1, complementary to mammalian CRH which prefers CRF1
- Cardiovascular: peripheral vasodilation via endothelial CRF2, reducing blood pressure; positive chronotropic effect at high doses
- Inhibits stress-axis acth/" class="wiki-internal-link">ACTH/cortisol release when given centrally in some species (CRF2-mediated stress resilience)
- Modulates appetite and food intake via hypothalamic CRF2 signaling; anorexigenic at central doses
- Fish: coordinates osmoregulation and cardiovascular adaptation to hypertonic environments in urophysis-pituitary axis
Research Findings
- UI was the first CRF family peptide used to establish CRF receptor pharmacology and define CRF2 subtype
- Antalarmin (CRF1 antagonist) does not block UI cardiovascular effects, confirming CRF2 mediation
- UI infusion in rodents produced greater hypotension than rat CRH at equimolar doses due to higher CRF2 potency
- Central UI reduced anxiety-like behavior in rat elevated-plus maze, supporting CRF2 anxiolysis hypothesis
- UI and sauvagine used as reference CRF2 agonists in drug discovery screens for heart failure and IBS
- UI analogs being developed for cardiac applications given CRF2-mediated positive inotropy in heart
Research Protocols
- CRF2 pharmacology tool: 1-100 nM UI in receptor binding or calcium mobilization assays
- In vivo hemodynamic: 0.1-10 nmol/kg IV in anesthetized rats; measure blood pressure and heart rate
- Central ICV injection: 0.1-1 nmol for appetite/stress studies in rodents
- Peripheral 50 ng/kg/min IV infusion for up to 60 minutes in rodent cardiac studies
- Not used clinically; research tool and reference peptide
Interactions
- Astressin-2B (CRF2 antagonist): blocks all cardiovascular and CNS effects of UI
- CRF-binding protein (CRF-BP): binds and sequesters UI, reducing bioavailability; relevant for CNS studies
- Urocortins (UCN1, 2, 3): endogenous mammalian CRF2 agonists with similar pharmacological profile to UI
Safety Profile
Research peptide only. Not used in humans. Well tolerated in rodent pharmacology studies at research doses. No clinical safety data.
Legal & Regulatory
Research peptide; not approved for clinical use
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