PMID- 17244889 OWN - NLM STAT- MEDLINE DCOM- 20070618 LR - 20181201 IS - 1931-857X (Print) IS - 1522-1466 (Linking) VI - 292 IP - 5 DP - 2007 May TI - Vesicular monoamine transporter 1 mediates dopamine secretion in rat proximal tubular cells. PG - F1592-8 AB - 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. FAU - Maurel, Agnes AU - Maurel A AD - Institut National de la Sante et de la Recherche Medicale U858 and Universite Toulouse III, Institut de Medecine Moleculaire de Rangueil, Toulouse, France. FAU - Spreux-Varoquaux, Odile AU - Spreux-Varoquaux O FAU - Amenta, Francesco AU - Amenta F FAU - Tayebati, Seyed Khosrow AU - Tayebati SK FAU - Tomassoni, Daniele AU - Tomassoni D FAU - Seguelas, Marie-Helene AU - Seguelas MH FAU - Parini, Angelo AU - Parini A FAU - Pizzinat, Nathalie AU - Pizzinat N LA - eng PT - Journal Article DEP - 20070123 PL - United States TA - Am J Physiol Renal Physiol JT - American journal of physiology. Renal physiology JID - 100901990 RN - 0 (Sodium Chloride, Dietary) RN - 0 (Vesicular Monoamine Transport Proteins) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Blotting, Western MH - Cells, Cultured MH - Dopamine/biosynthesis/*metabolism MH - Dose-Response Relationship, Drug MH - Immunohistochemistry MH - Kidney Tubules, Proximal/cytology/*metabolism MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sodium Chloride, Dietary/administration & dosage/pharmacology MH - Vesicular Monoamine Transport Proteins/metabolism/*physiology EDAT- 2007/01/25 09:00 MHDA- 2007/06/19 09:00 CRDT- 2007/01/25 09:00 PHST- 2007/01/25 09:00 [pubmed] PHST- 2007/06/19 09:00 [medline] PHST- 2007/01/25 09:00 [entrez] AID - 00514.2006 [pii] AID - 10.1152/ajprenal.00514.2006 [doi] PST - ppublish SO - Am J Physiol Renal Physiol. 2007 May;292(5):F1592-8. doi: 10.1152/ajprenal.00514.2006. Epub 2007 Jan 23.