The multidrug transporter MATE1 sequesters OCs within an intracellular compartment that has no influence on OC secretion in renal proximal tubules
| Autor: | William H. Dantzler, Kristen K. Evans, Lucy J. Martinez-Guerrero, Stephen H. Wright |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine 1-Methyl-4-phenylpyridinium Vacuolar Proton-Translocating ATPases medicine.medical_specialty Organic Cation Transport Proteins Physiology Endosome ATPase CHO Cells Endosomes Transfection Kidney Tubules Proximal 03 medical and health sciences chemistry.chemical_compound Cricetulus Internal medicine medicine Animals Secretion Fluorescent Dyes biology Vesicle Chinese hamster ovary cell Organic Cation Transporter 2 Bafilomycin Articles Renal Reabsorption Molecular biology Quaternary Ammonium Compounds Kinetics Renal Elimination 4-Chloro-7-nitrobenzofurazan 030104 developmental biology Endocrinology Microscopy Fluorescence chemistry Cytoplasm biology.protein Rabbits Intracellular |
| Zdroj: | American Journal of Physiology-Renal Physiology. 310:F57-F67 |
| ISSN: | 1522-1466 1931-857X |
| Popis: | Secretion of organic cations (OCs) across renal proximal tubules (RPTs) involves basolateral OC transporter (OCT)2-mediated uptake from the blood followed by apical multidrug and toxin extruder (MATE)1/2-mediated efflux into the tubule filtrate. Whereas OCT2 supports electrogenic OC uniport, MATE is an OC/H+exchanger. As assessed by epifluorescence microscopy, cultured Chinese hamster ovary (CHO) cells that stably expressed human MATE1 accumulated the fluorescent OC N, N, N-trimethyl-2-[methyl(7-nitrobenzo[c][l,2,5]oxadiazol-4-yl)amino]ethanaminium (NBD-MTMA) in the cytoplasm and in a smaller, punctate compartment; accumulation in human OCT2-expressing cells was largely restricted to the cytoplasm. A second intracellular compartment was also evident in the multicompartmental kinetics of efflux of the prototypic OC [3H]1-methyl-4-phenylpyridinium (MPP) from MATE1-expressing CHO cells. Punctate accumulation of NBD-MTMA was markedly reduced by coexposure of MATE1-expressing cells with 5 μM bafilomycin (BAF), an inhibitor of V-type H+-ATPase, and accumulation of [3H]MPP and [3H]NBD-MTMA was reduced by >30% by coexposure with 5 μM BAF. BAF had no effect on the initial rate of MATE1-mediated uptake of NBD-MTMA, suggesting that the influence of BAF was a secondary effect involving inhibition of V-type H+-ATPase. The accumulation of [3H]MPP by isolated single nonperfused rabbit RPTs was also reduced >30% by coexposure to 5 μM BAF, suggesting that the native expression in RPTs of MATE protein within endosomes can increase steady-state OC accumulation. However, the rate of [3H]MPP secretion by isolated single perfused rabbit RPTs was not affected by 5 μM BAF, suggesting that vesicles loaded with OCs+are not likely to recycle into the apical plasma membrane at a rate sufficient to provide a parallel pathway for OC secretion. |
| Databáze: | OpenAIRE |
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