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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/F1047    most recent 00074.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Kotlo, K. Articles by Danziger, R. S. Search for Related Content PubMed PubMed Citation Articles by Kotlo, K. Articles by Danziger, R. S.

Aminopeptidase N reduces basolateral Na⁺-K⁺-ATPase in proximal tubule cells

Departments of ¹Medicine, ²Physiology and Biophysics, and ³Pharmacology, University of Illinois at Chicago, Chicago; and ⁴Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois

Submitted 13 February 2007 ; accepted in final form 12 July 2007

Aminopeptidase N/CD13 (Anpep) is a membrane-bound protein that catalyzes the formation of natriuretic hexapeptide angiotensin IV (ANG IV) from ANG III. We previously reported that Anpep is more highly expressed in the kidneys of Dahl salt-resistant (SR/Jr) than salt-sensitive (SS/Jr) rats, Anpep maps to a quantitative trait locus for hypertension, and that the Dahl SR/Jr rat contains a functional polymorphism of the gene. This suggests that renal Anpep may be linked to salt sensitivity; however, its effect on renal Na handling has not been determined. Here, we examined regulation of basolateral Na⁺-K⁺-ATPase, a preeminent basolateral Na⁺ transporter in proximal tubule cells, by Anpep in LLC-PK1 cells. Treatment of the cells with Anpep siRNA increased total cellular Na⁺-K⁺-ATPase activity and basolateral Na⁺-K⁺-ATPase abundance by approximately twofold. Conversely, Anpep overexpression reduced Na⁺-K⁺-ATPase activity and basolateral abundance by 50%. Similar effects were observed after treatment with ANG IV (10 nM, x30 min and 12 h). ANG IV receptor (AGTRIV) knockdown via specific siRNA relieved the decreases in basolateral Na⁺-K⁺-ATPase levels and activity induced by Anpep overexpression. In sum, these results demonstrate that Anpep reduces basolateral Na⁺-K⁺-ATPase levels via ANG IV/AGTRIV signaling. This novel pathway may be important in renal adaptation to high salt.

angiotensin IV; kidney