Arginine Vasopressin Receptors

Arginine vasopressin (AVP) receptors

Arginine vasopressin regulates the volemic status in the human body. Normally hypo-osmolality suppresses the synthesis and release of AVP. Dysregulation of this suppression may cause hyponatremia. The physiological effects of arginine vasopressin are mediated through three receptor subtypes: V1A, V1B and V2. V2 activation by AVP is the key mechanism for renal water regulation, maintenance of total body volume and plasma tonicity. Aquaretics are a new class of drugs which can correct hyponatremia by direct competitive inhibition of AVP at V2 receptors, causing renal excretion of free water (free of electrolytes).

AVP receptors are G-protein coupled membrane receptors [1]. V1A receptors are vascular, V2 renal and V1B pituitary (also known as V3 receptors). The V1A receptors are thought to mediate the vasoconstrictive, mitogenic and possibly the platelet aggregative and hypercoagulable actions of arginine vasopressin.

Binding of AVP to V2 receptors in the renal collecting ducts activates adenylyl cyclase which produces cyclic AMP and subsequent activation of protein kinase A. This in turn leads to enhanced production of water channels aquaporin-2. These channels facilitate water reabsorption into the medullary interstitium. V2 receptor antagonists (vaptans)  are useful in the treatment of euvolemic and hypervolemic hyponatremia [2]. V1B (V3) receptor stimulation is associated with release of adrenocorticotropic hormone and beta endorphin.

References

1. Melissa A Wasilewski, Valerie D Myers, Fabio A Recchia, Arthur M Feldman, Douglas G Tilley. Arginine vasopressin receptor signaling and functional outcomes in heart failure. Cell Signal. 2016 Mar;28(3):224-233.
2. Robert W Schrier, Peter Gross, Mihai Gheorghiade, Tomas Berl, Joseph G Verbalis, Frank S Czerwiec, Cesare Orlandi, SALT Investigators. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006 Nov 16;355(20):2099-112.