Chemical Identity

Property	Value
Name	Vasopressin (Antidiuretic Hormone, ADH)
Source	Hypothalamus (supraoptic & paraventricular nuclei) → Posterior pituitary
Sequence	Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH₂
Abbreviation	CYFQNCPRG-NH₂
Length	9 amino acids (nonapeptide)
Chemical Formula	C₄₆H₆₅N₁₅O₁₂S₂
Molecular Weight	1084.2 Da
Disulfide Bond	Cys1-Cys6 (cyclic)
CAS Number	9034-50-8
PDB Structures	1JK6 (NMR)

Structure

Vasopressin is a cyclic nonapeptide, differing from oxytocin at positions 3 (Phe vs Ile) and 8 (Arg vs Leu):

Position	Oxytocin	Vasopressin	Function
3	Ile	Phe	Receptor selectivity
8	Leu	Arg	Receptor selectivity

Receptors

V1a Receptor (AVPR1A)

• Distribution: Vascular smooth muscle, liver, platelets, brain
• G-protein: Gαq → PLC → IP₃ + DAG
• Effects: Vasoconstriction, platelet aggregation, hepatic glycogenolysis

V1b Receptor (AVPR1B)

• Distribution: Anterior pituitary, brain, pancreas
• G-protein: Gαq → PLC → IP₃ + DAG
• Effects: ACTH release, glucose regulation

V2 Receptor (AVPR2)

• Distribution: Renal collecting duct (principal cells)
• G-protein: Gαs → cAMP → PKA
• Effects: Aquaporin-2 insertion, water reabsorption

Physiological Functions

Water Balance (V2-mediated)

Osmotic stimulus → Hypothalamic osmoreceptors → OT/SON neurons
    → AVP release → V2 receptor (kidney)
    → cAMP → PKA → AQP2 phosphorylation
    → AQP2 trafficking to apical membrane
    → Water reabsorption → Urine concentration

Blood Pressure (V1a-mediated)

• Vasoconstriction (potent)
• Hepatic glycogenolysis
• Platelet aggregation

Stress Response (V1b-mediated)

• ACTH release from anterior pituitary
• HPA axis modulation

Clinical Applications

Diabetes Insipidus

• Central DI: AVP deficiency → Desmopressin (DDAVP)
• Nephrogenic DI: V2 resistance → Thiazides, amiloride

Desmopressin (DDAVP)

Property	Value
Sequence	Cys-Tyr-Phe-Gln-Asn-Cys-Pro-D-Arg-Gly-NH₂
Modification	D-Arg at position 8
T½	1-2 hours (vs 15-20 min for native)
Selectivity	V2-selective (reduced V1a activity)
Indications	DI, nocturnal enuresis, hemophilia A/B, von Willebrand disease

Other Vasopressin Analogs

Drug	Modification	Indication
Terlipressin	N-terminal Lys-Arg extension	Hepatorenal syndrome, variceal bleeding
Vasopressin (Pitressin)	Native	GI bleeding, vasodilatory shock
Lypressin	D-Lys at position 8	Vasopressin analog
Felypressin	Phe² replacing Tyr²	Local vasoconstrictor

Manufacturing

• SPPS (Fmoc): Standard solid-phase synthesis
• Disulfide formation: Air oxidation or glutathione redox buffer
• Purification: RP-HPLC
• Desmopressin: D-Arg incorporation during synthesis

References

1. Knepper MA, et al. “Molecular physiology of water balance.” Annual Review of Physiology 66:625-657, 2004.
2. Jard S. “Mechanisms of action of vasopressin analogues.” Clinical Endocrinology 54:1-9, 2001.
3. Laszlo FA, et al. “Vasopressin: pharmacology, functions, and therapeutic potential.” Neuroscience 16:1-21, 2002.
4. Knepper MA. “Aquaporin-2: a molecular water channel.” Journal of the American Society of Nephrology 6:198-205, 1995.
5. Robertson GL. “Disorders of the posterior pituitary.” Endocrinology and Metabolism Clinics 30:751-773, 2001.