Abstract

The localization of the water channel aquaporin-2 (AQP2) is subjected to regulation by vasopressin. Vasopressin adjusts the amount of AQP2 in the plasma membrane by regulating its redistribution from intracellular vesicles into the plasma membrane allowing water entry into the cells and water exit through AQP3 and AQP4. This permits water reabsorption and urine concentration. Following binding of vasopressin to its V2R receptor, the rise in cAMP activates protein kinase A, which in turn phosphorylates AQP2 and thereby triggers the redistribution of AQP2. Several proteins participating in the control of cAMP-dependent AQP2 trafficking have been identified including SNAREs, annexin-2, hsc70, AKAPs and small GTPases of the Rho family proteins. Moreover, AQP2 has been found to be regulated by posttranslational modifications (PTMs), such as ubiquitination and glutathionylation. Loss-of-function mutations of both V2R and AQP2 are associated with congenital nephrogenic diabetes insipidus characterized by a failure to concentrate urine. Conversely gain-of-function mutations of the V2R are associated with the nephrogenic syndrome of inappropriate antidiuresis characterized by positive water balance and hyponatremia. Vaptans, nonpeptide vasopressin receptor antagonists represent a new class of drugs developed for the treatment of euvolemic or hypervolemic hyponatremia. This chapter summarizes recent data elucidating molecular mechanisms underlying the trafficking of AQP2. The mechanism of action of vaptans and their current use in clinical practice is discussed.

Autore Pugliese

• Valenti Giovanna , Tamma Grazia

Tutti gli autori

• VALENTI G.;TAMMA G.

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Anno di pubblicazione

2015

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