Demonstration of the functional impact of vasopressin signalling in thick ascending limb by a targeted transgenic rat approach.

Demonstration of the functional impact of vasopressin signalling in thick ascending limb by a targeted transgenic rat approach. Am J Physiol Renal Physiol. 2016 Jun 15;:ajprenal.00126.2016 Authors: Mutig K, Borowski T, Boldt C, Borschewski A, Paliege A, Popova E, Bader M, Bachmann S Abstract The antidiuretic hormone vasopressin (AVP) regulates renal salt and water reabsorption along the distal nephron and collecting duct system. These effects are mediated by V2 receptors (V2R) and release of intracellular Gs-mediated cAMP to activate epithelial transport proteins. Inactivating mutations in the V2R gene lead to the X-linked form of nephrogenic diabetes insipidus (NDI) which has chiefly been related with impaired aquaporin 2-mediated water reabsorption in the collecting ducts. Previous work also suggested the AVP-V2R-mediated activation of Na+-K+-2Cl--cotransporters (NKCC2) along the thick ascending limb (TAL) in the context of urine concentration, but its individual contribution to NDI or, more generally, to overall renal function was unclear. We hypothesized that V2R-mediated effects in TAL essentially determine its reabsorptive function. To test this, we reevaluated V2R expression. Basolateral membranes of medullary and cortical TAL were clearly stained, whereas cells of the macula densa cells were unreactive. A dominant-negative, NDI-causing truncated V2R mutant (Ni3-Glu242 stop) was then introduced into the rat genome under contro...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research