V2 vasopressin receptor deficiency causes changes in expression and function of renal and hypothalamic components involved in electrolyte and water homeostasis

American Journal of Physiology. Renal Physiology
Nicole SchliebeKatrin Sangkuhl

Abstract

Polyuria, hypernatremia, and hypovolemia are the major clinical signs of inherited nephrogenic diabetes insipidus (NDI). Hypernatremia is commonly considered a secondary sign caused by the net loss of water due to insufficient insertion of aquaporin-2 water channels into the apical membrane of the collecting duct cells. In the present study, we employed transcriptome-wide expression analysis to study gene expression in V2 vasopressin receptor (Avpr2)-deficient mice, an animal model for X-linked NDI. Gene expression changes in NDI mice indicate increased proximal tubular sodium reabsorption. Expression of several key genes including Na+-K+-ATPase and carbonic anhydrases was increased at the mRNA levels and accompanied by enhanced enzyme activities. In addition, altered expression was also observed for components of the eicosanoid and thyroid hormone pathways, including cyclooxygenases and deiodinases, in both kidney and hypothalamus. These effects are likely to contribute to the clinical NDI phenotype. Finally, our data highlight the involvement of the renin-angiotensin-aldosterone system in NDI pathophysiology and provide clues to explain the effectiveness of diuretics and indomethacin in the treatment of NDI.

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Citations

Nov 26, 2010·The Journal of Biological Chemistry·Ines LiebscherAngela Schulz
May 28, 2011·BMC Biochemistry·Johannes LaknerTorsten Schöneberg
Mar 26, 2014·PloS One·Kathy BusseJohannes Schwarz
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Jan 17, 2015·Journal of Cellular and Molecular Medicine·Leonilde BonfratePiero Portincasa
Nov 11, 2017·International Journal of Molecular Sciences·Serena MilanoGiuseppe Procino
Apr 16, 2010·Physiological Reviews·Hayo CastropCharlotte Wagner
Apr 13, 2019·Clinical Kidney Journal·Sonia SharmaDetlef Bockenhauer
Oct 3, 2018·Aging and Disease·Stefanie HardtIrmgard Tegeder
May 18, 2019·Journal of the American Society of Nephrology : JASN·Torsten GieseckeKerim Mutig

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