Urocortin

Chemical Identity

Property	Value
Name	Urocortin
Sequence	Ser-Ala-His-Leu-Gly-Lys-Leu-Gln-Asp-Ile-Ala-His-Leu-Gln-Val-Leu-Arg-Arg-Glu-Phe-Arg-Lys-Glu-Lys-Leu-Ala-Glu-Ile-Ala-Ala-Tyr-Gln-Gln-Leu-Gly-Glu-Ser-Thr
Length	40 amino acids
Homology	43% identical to human CRH
MW	4497.1 Da
Receptor	CRH-R2 (high affinity)

Receptor Selectivity

Peptide	CRH-R1	CRH-R2
CRH	High	Low
Urocortin	High	High
Urocortin-2	Low	High
Urocortin-3	Low	High

Physiological Functions

Stress Response

• Urocortin is co-expressed with CRH in stress-responsive neurons
• Activates both CRH-R1 and CRH-R2
• May mediate the anxiolytic (anti-anxiety) component of the stress response

Feeding

• Central injection suppresses feeding (via CRH-R1 and CRH-R2)
• Less potent than CRH at suppressing feeding

Cardiovascular

• Vasodilation: Potent vasodilator (via CRH-R2)
• Blood pressure: Reduces mean arterial pressure
• Cardiac: Increases heart rate

Other Functions

• GI motility: Modulates intestinal motility
• Immune: Anti-inflammatory effects
• Neuroprotection: Protects neurons from excitotoxicity

Clinical Significance

Urocortin 2 and 3

• Urocortin-2: Selective CRH-R2 agonist, cardiovascular regulation
• Urocortin-3: Selective CRH-R2 agonist, reproductive function

Therapeutic Potential

• Heart failure: Urocortin improves cardiac output
• Depression: CRH-R2 modulation may have antidepressant effects
• IBS: Urocortin modulates visceral pain

Manufacturing

• SPPS (Fmoc): Standard solid-phase synthesis
• Purification: RP-HPLC
• Characterization: Mass spectrometry, NMR

References

1. Vaughan J, et al. “Urocortin, a mammalian neuropeptide related to fish urotensin I and corticotropin-releasing factor.” Nature 378:287-292, 1995. doi:10.1073/pnas.92.23.10455
2. Lewis K, et al. “Identification of urocortin III, a second member of the urocortin family.” Proceedings of the National Academy of Sciences 97:14394-14399, 2000.
3. Reyes TM, et al. “Urocortin II: a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by the CRF type 2 receptor.” Proceedings of the National Academy of Sciences 97:14394-14399, 2000.
4. Hsu SY, Hsueh AJ. “Human stresscopin and urocortin II are selective agonists for the type 2 corticotropin-releasing hormone receptor.” Nature Medicine 7:1047-1049, 2001.
5. Bale TL, Vale WW. “CRF and CRF receptors: role in stress responsivity, behavior, and neuroendocrine function.” Neuroscience 126:289-318, 2004.