HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/4/F740    most recent 00380.2004v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (18) Citing Articles via Google Scholar Google Scholar Articles by Bacic, D. Articles by Murer, H. Search for Related Content PubMed PubMed Citation Articles by Bacic, D. Articles by Murer, H.

Activation of dopamine D₁-like receptors induces acute internalization of the renal Na⁺/phosphate cotransporter NaPi-IIa in mouse kidney and OK cells

Institutes of ¹Physiology and ²Anatomy, University of Zurich, Zurich, Switzerland; and Departments of ³Internal Medicine and ⁴Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas

Submitted 12 October 2004 ; accepted in final form 13 November 2004

The Na⁺/phosphate cotransporter NaPi-IIa (SLC34A1) is the major transporter mediating the reabsorption of P_i in the proximal tubule. Expression and activity of NaPi-IIa is regulated by several factors, including parathyroid hormone, dopamine, metabolic acidosis, and dietary P_i intake. Dopamine induces natriuresis and phosphaturia in vivo, and its actions on several Na⁺-transporting systems such as NHE3 and Na⁺-K⁺-ATPase have been investigated in detail. Using freshly isolated mouse kidney slices, perfused proximal tubules, and cultured renal epithelial cells, we examined the acute effects of dopamine on NaPi-IIa expression and localization. Incubation of isolated kidney slices with the selective D₁-like receptor agonists fenoldopam (10 µM) and SKF-38393 (10 µM) for 1 h induced NaPi-IIa internalization and reduced expression of NaPi-IIa in the brush border membrane (BBM). The D₂-like selective agonist quinpirole (1 µM) had no effect. The D₁ and D₂ agonists did not affect the renal Na⁺/sulfate cotransporter NaSi in the BBM of the proximal tubule. Studies with isolated perfused proximal tubules demonstrated that activation of luminal, but not basolateral, D₁-like receptors caused NaPi-IIa internalization. In kidney slices, inhibition of PKC (1 µM chelerythrine) or ERK1/2 (20 µM PD-098089) pathways did not prevent the fenoldopam-induced internalization. Inhibition with the PKA blocker H-89 (10 µM) abolished the effect of fenoldopam. Immunoblot demonstrated a reduction of NaPi-IIa protein in BBMs from kidney slices treated with fenoldopam. Incubation of opossum kidney cells transfected with NaPi-IIa-green fluorescent protein chimera shifted fluorescence from the apical membrane to an intracellular pool. In summary, dopamine induces internalization of NaPi-IIa by activation of luminal D₁-like receptors, an effect that is mediated by PKA.

protein kinase A; proximal tubule; brush border membrane

This article has been cited by other articles:

				R. Cunningham, R. Biswas, M. Brazie, D. Steplock, S. Shenolikar, and E. J. Weinman Signaling pathways utilized by PTH and dopamine to inhibit phosphate transport in mouse renal proximal tubule cells Am J Physiol Renal Physiol, February 1, 2009; 296(2): F355 - F361. [Abstract] [Full Text] [PDF]

				C. Zeng, I. Armando, Y. Luo, G. M. Eisner, R. A. Felder, and P. A. Jose Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension: studies in dopamine receptor knockout mice Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H551 - H569. [Abstract] [Full Text] [PDF]

				M. Donowitz and X. Li Regulatory Binding Partners and Complexes of NHE3 Physiol Rev, July 1, 2007; 87(3): 825 - 872. [Abstract] [Full Text] [PDF]

				P. Capuano, D. Bacic, M. Roos, S. M. Gisler, G. Stange, J. Biber, B. Kaissling, E. J. Weinman, S. Shenolikar, C. A. Wagner, et al. Defective coupling of apical PTH receptors to phospholipase C prevents internalization of the Na+-phosphate cotransporter NaPi-IIa in Nherf1-deficient mice Am J Physiol Cell Physiol, February 1, 2007; 292(2): C927 - C934. [Abstract] [Full Text] [PDF]

				M. A. Lanaspa, H. Giral, S. Y. Breusegem, N. Halaihel, G. Baile, J. Catalan, J. A. Carrodeguas, N. P. Barry, M. Levi, and V. Sorribas Interaction of MAP17 with NHERF3/4 induces translocation of the renal Na/Pi IIa transporter to the trans-Golgi Am J Physiol Renal Physiol, January 1, 2007; 292(1): F230 - F242. [Abstract] [Full Text] [PDF]

				C. Zeng, Z. Wang, H. Li, P. Yu, S. Zheng, L. Wu, L. D. Asico, U. Hopfer, G. M. Eisner, R. A. Felder, et al. D3 Dopamine Receptor Directly Interacts With D1 Dopamine Receptor in Immortalized Renal Proximal Tubule Cells Hypertension, March 1, 2006; 47(3): 573 - 579. [Abstract] [Full Text] [PDF]