Desmopressin

Desmopressin exerts its effects at the molecular level by binding to G-protein-coupled V2 receptors located on the basolateral membrane of the distal convoluted tubules and collecting ducts of the kidney.

Upon binding to the V2 receptor, desmopressin stimulates the enzyme adenylate cyclase, which increases intracellular levels of cyclic AMP (cAMP). This signaling cascade triggers the phosphorylation and translocation of aquaporin-2 (AQP2) water channels from intracellular vesicles to the apical (luminal) cell membrane. These channels allow water to flow passively from the renal tubule back into the systemic circulation, thereby concentrating the urine and maintaining fluid homeostasis.

In the vascular endothelium, desmopressin stimulates V2 receptors that trigger the release of von Willebrand factor (vWF) from the Weibel-Palade bodies of endothelial cells. The released vWF subsequently stabilizes and protects Factor VIII in the plasma, effectively increasing the available pool of clotting factors required for primary hemostasis.

In the context of primary nocturnal enuresis, desmopressin's action is primarily peripheral (renal); however, research has explored its ability to influence the circadian rhythm of AVP secretion in the central nervous system to help normalize nighttime urine production.