[Lys8] Vasopressin

Vasopressin, also known as antidiuretic hormone (ADH), is a nonapeptide neurohormone essential for regulating the body’s fluid balance, blood pressure, and cardiovascular homeostasis. In most mammals, including pigs and some marsupials, the naturally occurring form includes a lysine at position 8, termed Lys⁸-vasopressin. This peptide plays a central role in maintaining extracellular fluid tonicity, responding to subtle changes in serum osmolality and blood volume. Its wide physiological impact - from renal water reabsorption to vascular tone modulation - makes vasopressin one of the most studied and clinically relevant peptide hormones in biology and medicine.

Molecular Details
- Sequence: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Lys-Gly-NH₂, Disulfide bridge Cys1-Cys6
- Length: 9 amino acids
- Structure: Cyclic peptide with a disulfide bond between Cys1 and Cys6, essential for receptor binding
- Receptors: Interacts with G protein-coupled receptors V1a, V1b (V3), and V2
- Receptor Distribution: V1a in vascular smooth muscle and liver, V2 in renal collecting ducts, and V1b in the pituitary gland.

Functional Roles & Mechanisms
Vasopressin’s principal actions arise through receptor-specific signaling cascades:

- V2 Receptors: In the kidney, binding triggers cAMP-mediated insertion of aquaporin-2 water channels into collecting duct membranes, enhancing water reabsorption and reducing urine volume, thus conserving body water and adjusting serum osmolality.

- V1a Receptors: Activation in vascular smooth muscle promotes vasoconstriction, increasing systemic vascular resistance and blood pressure — particularly important under stress, hypovolemia, or hypotensive states.

- V1b Receptors: Expressed in the pituitary gland, regulating ACTH release and stress axis dynamics. Collectively, these pathways allow vasopressin to coordinate renal, cardiovascular, and neuroendocrine responses to osmotic and hemodynamic challenges.

Physiological & Pathophysiological Significance
Vasopressin is central to fluid balance and blood pressure control. Dysregulation can contribute to conditions such as: -

Diabetes Insipidus (DI): Low or absent vasopressin leads to excessive water loss, polyuria, and thirst. :

- SIADH (Syndrome of Inappropriate Antidiuretic Hormone): Excessive vasopressin release causes water retention and hyponatremia, with clinical sequelae including nausea, confusion, and seizures.

- Critical Illness & Shock: Vasopressin and its analogues are used in acute care to support blood pressure in vasodilatory shock states.

Applications in Research
As a research reagent, Lys⁸-vasopressin is used to:

- Study renal physiology, including aquaporin trafficking and V2 receptor signaling.

- Explore vascular biology and vasoconstriction mechanisms via V1a receptors.

- Investigate neuroendocrine stress pathways and hormonal regulation through V1b.

- Validate and benchmark novel vasopressin receptor agonists/antagonists in preclinical models of sepsis, heart failure, and water balance disorders.

- Model central effects on social behavior, circadian rhythms, and stress responses in neuroscience research.

Research Insights & Therapeutic Potential
Beyond classical water homeostasis, emerging research links vasopressin signaling to pathologies such as chronic heart failure, polycystic kidney disease, and certain neuropsychiatric conditions. Targeted modulation of vasopressin receptors — including selective V2 agonists such as desmopressin or V1a/V2 antagonists (vaptans) — offers therapeutic strategies across a spectrum of disorders in which fluid balance and vascular tone are disrupted.

Lys⁸-vasopressin is a versatile and biologically potent peptide with deep scientific and clinical relevance. Used in fundamental physiology studies, translational research, and receptor pharmacology, this peptide remains indispensable for investigations into fluid and cardiovascular regulation, endocrine signaling, and receptor-targeted drug discovery.