Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption

Abstract

To prevent dehydration, terrestrial animals and humans have developed a sensitive and versatile system to maintain their water homeostasis. In states of hypernatremia or hypovolemia, the antidiuretic hormone vasopressin (AVP) is released from the pituitary and binds its type-2 receptor in renal principal cells. This triggers an intracellular cAMP signaling cascade, which phosphorylates aquaporin-2 (AQP2) and targets the channel to the apical plasma membrane. Driven by an osmotic gradient, prourinary water then passes the membrane through AQP2 and leaves the cell on the basolateral side via AQP3 and AQP4 water channels. When water homeostasis is restored, AVP levels decline, and AQP2 is internalized from the plasma membrane, leaving the plasma membrane watertight again. The action of AVP is counterbalanced by several hormones like prostaglandin E2, bradykinin, dopamine, endothelin-1, acetylcholine, epidermal growth factor, and purines. Moreover, AQP2 is strongly involved in the pathophysiology of disorders characterized by renal concentrating defects, as well as conditions associated with severe water retention. This review focuses on our recent increase in understanding of the molecular mechanisms underlying AVP-regulated renal water transport in both health and disease.

Validation of an integrative mathematical model of dehydration and rehydration in virtual humans

“…1994), and AVP binding to AVPR2 causes AQP2 to move to the basolateral surface of tubule cells. Hence, AVP increases the numbers of active (basolaterally expressed) and inactive (cytosolic) AQP2 (Boone and Deen 2008). For simplicity, we assume that both pools are affected equally by AVP, and that the effects track changes in AVP levels instantly.…”

Lithium in Kidney Diseases

“…In renal principal cells, AVP regulates the expression of aquaporin-2 (AQP-2) water channel and its apical membrane insertion, leading to water reabsorption in the collecting duct and concentrated urine. 16 Two major effects of lithium on collecting duct-downregulating AQP-2 expression and reducing the number of renal principal cells-have been suggested to contribute to NDI. 4 Consistent with previous reports, 17 de Groot et al showed that lithium induced downregulation of AQP-2 both in cultured murine principal collecting-duct cells and in kidneys.…”

A molecularly guided tour along the nephron

“…In recent years, our understanding of the molecular nature of these transport proteins has made major progress through the application of functional expression cloning techniques using Xenopus laevis oocytes and the identification of gene defects in inherited renal tubular transport disorders. The regulation of these transport processes is constantly challenged by a demanding and greatly variable environment including an acidic luminal pH, a high medullary osmolarity, and a variability in blood and urinary flow as well as in the composition of the prourine [4]. The activity of these transporters can basically be controlled at several discrete levels.…”

“…The largest fraction of the glomerular filtrate is retrieved in the proximal tubule that reabsorbs among others Na + , K + , Ca 2+ , Cl − , HCO 3 − , PO 4 3− , glucose, amino acids, and water. The Na + ,H + exchanger, one of the major luminal transporters, is accommodating many transport processes in this nephron segment.…”

“…Vesicular Cl − /H + exchangers are expressed in the proximal tubule, and malfunction of these proteins impairs the endocytosis process in this segment explaining the primary defect in Dent's disease as outlined by Jentsch and coworkers [11]. The article by Biber et al addresses the regulatory mechanisms controlling the activity of the Na + -PO 4 3− cotransporters present in the apical membrane of the proximal tubule [2]. Finally, Verrey et al review the transcellular amino acid transport machinery in great molecular detail illuminating the importance for overall amino acid conservation as well as for cellular housekeeping functions [16].…”