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This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/F1110    most recent 90336.2008v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Khan, F. Articles by Aperia, A. Search for Related Content PubMed PubMed Citation Articles by Khan, F. Articles by Aperia, A.

Negative reciprocity between angiotensin II type 1 and dopamine D1 receptors in rat renal proximal tubule cells

Farah Khan, Zuzana picarová, Sergey Zelenin, Ulla Holtbäck, Lena Scott, and Anita Aperia

Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, SE-171 76 Stockholm, Sweden

Submitted 30 May 2008 ; accepted in final form 6 August 2008

Sodium excretion is bidirectionally regulated by dopamine, acting on D1-like receptors (D1R) and angiotensin II, acting on AT₁ receptors (AT1R). Since sodium excretion has to be regulated with great precision within a short frame of time, we tested the short-term effects of agonist binding on the function of the reciprocal receptor within the D1R-AT1R complex in renal proximal tubule cells. Exposure of rat renal proximal tubule cells to a D1 agonist was found to result in a rapid partial internalization of AT1R and complete abolishment of AT1R signaling. Similarly, exposure of rat proximal tubule cells and renal tissue to angiotensin II resulted in a rapid partial internalization of D1R and abolishment of D1R signaling. D1R and AT1R were, by use of coimmunoprecipitation studies and glutathione-S-transferase pull-down assays, shown to be partners in a multiprotein complex. Na⁺-K⁺-ATPase, the target for both receptors, was included in this complex, and a region in the COOH-terminal tail of D1R (residues 397-416) was found to interact with both AT1R and Na⁺-K⁺-ATPase. Results indicate that AT1R and D1R function as a unit of opposites, which should provide a highly versatile and sensitive system for short-term regulation of sodium excretion.

AT₁ receptors; Na⁺-K⁺-ATPase; calcium signaling