Vasopressin

Overview

Vasopressin, also known as arginine vasopressin (AVP) or antidiuretic hormone (ADH), is a cyclic nonapeptide synthesized primarily in the magnocellular neurons of the supraoptic and paraventricular nuclei of the hypothalamus. It is transported to the posterior pituitary axon terminals and released into the systemic circulation in response to increased plasma osmolality, decreased blood volume, and decreased blood pressure. Vasopressin was among the first peptide hormones to be synthesized, with du Vigneaud achieving this milestone in 1953.

Structure

Vasopressin is a 9-amino acid peptide with the sequence Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2. The two cysteine residues at positions 1 and 6 form an intramolecular disulfide bond, creating a six-membered ring (tocin ring) essential for biological activity. The arginine residue at position 8 distinguishes AVP from oxytocin, which contains a leucine at the equivalent position. Despite 90% sequence homology with oxytocin, this single amino acid substitution confers distinct receptor selectivity profiles.

Receptor System

Vasopressin acts through three G-protein-coupled receptor subtypes:

• V1a receptors: Coupled to Gq and phospholipase C, mediating vasoconstriction through intracellular calcium mobilization. Expressed on vascular smooth muscle, hepatocytes, and platelets.
• V1b (V3) receptors: Found in the anterior pituitary, where vasopressin potentiates ACTH release. Also expressed in the brain, where it modulates stress responses and memory.
• V2 receptors: Coupled to Gs and adenylyl cyclase, expressed on the basolateral membrane of renal collecting duct principal cells. Activation stimulates aquaporin-2 (AQP2) insertion into the apical membrane, increasing water permeability.

Physiological Functions

The antidiuretic action of vasopressin is its primary physiological role. By promoting water reabsorption through AQP2 channels, vasopressin concentrates the urine and dilutes the plasma, maintaining osmotic homeostasis. V1a receptor activation produces systemic vasoconstriction, contributing to blood pressure regulation during hemorrhage.

Central vasopressin signaling modulates complex social behaviors, including pair bonding, paternal behavior, and social recognition. Comparative studies in voles demonstrate that species differences in vasopressin receptor distribution in the brain correlate with variations in social monogamy and parental care.

Clinical Significance

Central diabetes insipidus results from insufficient vasopressin secretion, leading to polyuria and polydipsia. Nephrogenic diabetes insipidus arises from renal resistance to vasopressin, often due to V2 receptor or AQP2 mutations. The V2 receptor antagonist tolvaptan is approved for the treatment of syndrome of inappropriate antidiuretic hormone secretion (SIADH) and autosomal dominant polycystic kidney disease.