From the Guidelines
Vasopressin acts on V1a, V1b, V2, oxytocin, and purinergic receptors, with V1a receptors mediating vasoconstriction, V1b receptors involved in ACTH release, and V2 receptors regulating anti-diuretic effects. The action of vasopressin on these receptors is crucial for its physiological effects, including blood pressure regulation, water conservation, and stress responses 1. The V1a receptors are primarily found in vascular smooth muscle, where they mediate vasoconstriction through phospholipase C activation and intracellular calcium release. In contrast, V2 receptors are located in the renal collecting ducts, where they regulate water reabsorption by triggering the insertion of aquaporin-2 water channels into the cell membrane through cAMP-dependent mechanisms. The V1b receptors are mainly found in the anterior pituitary and modulate ACTH release.
Some of the key effects of vasopressin on its receptors include:
- Vasoconstriction mediated by V1a receptors, which is catecholamine-independent and complements norepinephrine in septic shock 1
- Anti-diuretic effects mediated by V2 receptors, which become apparent later in septic shock recovery 1
- ACTH release mediated by V1b receptors, which is involved in stress responses
- Vasodilatory effects mediated by oxytocin receptors, which may contribute to vasopressin's paradoxical induction of nitric oxide synthesis 1
The clinical importance of vasopressin's receptor specificity is evident in its therapeutic use, such as in vasodilatory shock (targeting V1 receptors) or diabetes insipidus (targeting V2 receptors) 1. Highly selective V1a agonists, such as selepressin, may have better effects in septic shock than vasopressin due to their narrow focus on the V1a receptor, minimizing V2 anti-diuresis and von Willebrand factor release 1.
From the FDA Drug Label
Vasopressin causes vasoconstriction by binding to V1 receptors on vascular smooth muscle coupled to the Gq/11-phospholipase C-phosphatidyl-inositol-triphosphate pathway, resulting in the release of intracellular calcium. In addition, vasopressin stimulates antidiuresis via stimulation of V2 receptors which are coupled to adenyl cyclase. At lower concentrations typical for the antidiuretic hormone vasopressin inhibits water diuresis via renal V2 receptors. In addition, vasopressin has been demonstrated to cause vasodilation in numerous vascular beds that are mediated by V2, V3, oxytocin and purinergic P2 receptors Vasopressin at pressor doses triggers contractions of smooth muscles in the gastrointestinal tract mediated by muscular V1-receptors and release of prolactin and ACTH via V3 receptors
Vasopressin acts on the following receptors:
- V1 receptors: causing vasoconstriction and contractions of smooth muscles in the gastrointestinal tract
- V2 receptors: stimulating antidiuresis, inhibiting water diuresis, and mediating vasodilation
- V3 receptors: mediating release of prolactin and ACTH 2
From the Research
Vasopressin Receptors
Vasopressin acts on several receptors, including:
- V1 vascular receptors
- V2 renal receptors
- V3 pituitary receptors
- Oxytocin receptors
- P2 class of purinoreceptors 3, 4
Receptor-Mediated Effects
The effects of vasopressin on its receptors include:
- Increase in water permeability in the collecting duct (via AQP2) mediated by V2 receptors 5
- Increase in urea permeability in the terminal inner medullary collecting duct (via UT-A1) mediated by V2 receptors 5
- Stimulation of sodium reabsorption in the cortical and outer medullary collecting duct (via ENaC) mediated by V2 receptors 5
- Reduction of blood flow to the inner medulla mediated by V1a receptors 5
Tissue Distribution
The tissue distribution of vasopressin receptors includes: