Submitted on October 8, 2007
Accepted on July 23, 2008
V2 vasopressin receptor-deficiency causes changes in expression and function of renal and hypothalamic components involved in electrolyte and water homeostasis
Nicole Schliebe1, Rainer Strotmann1, Kathy Busse2, Doreen Mitschke1, Heike Biebermann3, Lutz Schomburg4, Josef Kohrle4, Jorg Bar1, Holger Rompler1, Jurgen Wess5, Torsten Schoneberg6*, and Katrin Sangkuhl1
1 Medical Faculty, University of Leipzig, Institute of Biochemistry, Leipzig, Saxony, Germany
2 Institute of Biochemistry, Medical Faculty, University of Leipzig, Leipzig, Germany
3 Charite, Medical Faculty, Humboldt University Berlin, Institute of Experimental Pediatric Endocrinology, Berlin, Germany
4 Medical Faculty, Humboldt University Berlin, Institute of Experimental Endocrinology, Berlin, Berlin, Germany
5 United States; NIDDK, NIH, Laboratory of Bioorganic Chemistry, Bethesda, Maryland, United States
6 Medical Faculty, University of Leipzig, Institute of Biochemistry, Leipzig, Saxony, Germany; , Germany
* To whom correspondence should be addressed. E-mail: schoberg{at}medizin.uni-leipzig.de.
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.
