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This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/F1592    most recent 00514.2006v1 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 Google Scholar Google Scholar Articles by Maurel, A. Articles by Pizzinat, N. Search for Related Content PubMed PubMed Citation Articles by Maurel, A. Articles by Pizzinat, N.

Vesicular monoamine transporter 1 mediates dopamine secretion in rat proximal tubular cells

¹Institut National de la Santé et de la Recherche Médicale U858 and Université Toulouse III, Institut de Médecine Moléculaire de Rangueil, Toulouse and ²Université de Versailles Saint-Quentin-en-Yvelines, Faculté de Médecine Paris Ile de France Ouest, and Département de Biologie et Pharmacologie, Centre Hospitalier de Versailles, Le Chesnay, France; and ³Dipartimento di Medicina Sperimentale e Sanità Pubblica, Università di Camerino, Camerino, Italy

Submitted 22 December 2006 ; accepted in final form 3 January 2007

Renal dopamine, synthesized by proximal tubules, plays an important role in the regulation of renal sodium excretion. Although the renal dopaminergic system has been extensively investigated in both physiological and pathological situations, the mechanisms whereby dopamine is stored and secreted by proximal tubule cells remain obscure. In the present study we investigated whether vesicular monoamine transporters (VMAT)-1 and -2, which participate in amine storing and secretion, are expressed in rat renal proximal tubules, and we defined their involvement in dopamine secretion. By combining RT-PCR, Western blot, and immunocytochemistry we showed that VMAT-1 is the predominant isoform expressed in isolated proximal tubule cells. These results were confirmed by immunohistochemistry analysis of rat renal cortex showing that VMAT-1 was found in proximal tubules but not in glomeruli. Functional studies showed that, as previously reported for VMAT-dependent amine transporters, dopamine release by cultured proximal tubule cells was partially inhibited by disruption of intracellular H⁺ gradient. In addition, dopamine secretion was prevented by the VMAT-1/VMAT-2 inhibitor reserpine but not by the VMAT-2 inhibitor tetrabenazine. Finally, we demonstrated that tubular VMAT-1 mRNA and protein expression were significantly upregulated during a high-sodium diet. In conclusion, our results show for the first time the expression of a VMAT in the renal proximal tubule and its involvement in regulation of dopamine secretion. These data represent the first step toward the comprehension of the role of this transporter in renal dopamine handling and its involvement in pathological situations.

kidney; proximal tubules