Cyclophosphamide-induced vasopressin-independent activation of aquaporin-2 in the rat kidney.
Cyclophosphamide-induced vasopressin-independent activation of aquaporin-2 in the rat kidney.
Am J Physiol Renal Physiol. 2015 Jun 24;:ajprenal.00477.2014
Authors: Kim S, Choi HJ, Jo CH, Park JS, Kwon TH, Kim GH
Abstract
Because cyclophosphamide-induced hyponatremia was reported to occur without changes in plasma vasopressin in a patient with central diabetes insipidus, we hypothesized that cyclophosphamide or its active metabolite, 4-hydroperoxycyclophosphamide (4-HC), may directly dysregulate the expression of water channels or sodium transporters in the kidney. To investigate whether intrarenal mechanisms for urinary concentration are activated in vivo and in vitro by treatment with cyclophosphamide and 4-HC, respectively, we used water-loaded male Sprague-Dawley rats, primary cultured inner medullary collecting duct (IMCD) cells, and IMCD suspensions prepared from male Sprague-Dawley rats. In cyclophosphamide-treated rats, significant increases in renal expression of aquaporin-2 (AQP2) and Na-K-2Cl cotransporter type 2 (NKCC2) were shown by immunoblot analysis and immunohistochemistry. Apical translocation of AQP2 was also demonstrated by quantitative immunocytochemistry. In both rat kidney and primary cultured IMCD cells, significant increases in AQP2 and vasopressin receptor type 2 (V2R) mRNA expression were demonstrated by real-time quantitative PCR analysis. Confocal laser scanning microscopy revealed that apical translocatio...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Kim S, Choi HJ, Jo CH, Park JS, Kwon TH, Kim GH Tags: Am J Physiol Renal Physiol Source Type: research
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