The dopamine precursor L-dihydroxyphenylalanine is transported by the amino acid transporters rBAT and LAT2 in renal cortex

Henry Quiñones, Roberto Collazo, Orson W. Moe

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30 Citations (Scopus)

Abstract

The intrarenal autocrine-paracrine dopamine (DA) system is critical for Na+ homeostasis. L-Dihydroxyphenylalanine (L-DOPA) uptake from the glomerular filtrate and plasma provides the substrate for DA generation by the renal proximal tubule. The transporter(s) responsible for proximal tubule L-DOPA uptake has not been characterized. Renal cortical poly-A+ RNA injected into Xenopus laevis oocytes induced L-DOPA uptake in a time- and dose-dependent fashion with biphasic kms in the millimolar and micromolar range and independent of inward Na+, K+, of H+ gradients, suggesting the presence of low- and high-affinity L-DOPA carriers. Complementary RNA from two amino acid transporters yielded L-DOPA uptake significantly above water-injected controls the rBATP o.+ AT dimer (rBAT) and the LAT2/4F2 dimer (LAT2). In contradistinction to renal cortical poly-A+, L-DOPA kinetics of rBAT and LAT2 showed classic Michaelis-Menton kinetics with Kms in the micromolar and millimolar range, respectively. Sequence-specific antisense oligonucleotides to rBAT or LAT2 (AS) caused inhibition of rBAT and LAT2 cRNA-induced L-DOPA transport and cortical poly-A+-induced arginine and phenylalanine transport. However, the same ASs only partially blocked poly-A+-induced L-DOPA transport. In cultured kidney cells, silencing inhibitory RNA (siRNA) to rBAT significantly inhibited L-DOPA uptake. We conclude that rBAT and LAT2 can mediate apical and basolateral L-DOPA uptake into the proximal tubule, respectively. Additional L-DOPA transport mechanisms exist in the renal cortex that remain to be identified.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume287
Issue number1 56-1
DOIs
StatePublished - Jul 2004

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Amino Acid Transport Systems
Dihydroxyphenylalanine
Dopamine
Kidney
Poly A
Complementary RNA
Proximal Kidney Tubule
Antisense Oligonucleotides
Xenopus laevis
RNA Interference
Phenylalanine
Oocytes
Arginine
Cultured Cells
Homeostasis

Keywords

  • Amino acid transport
  • Proximal tubule
  • Sodium balance

ASJC Scopus subject areas

  • Physiology

Cite this

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title = "The dopamine precursor L-dihydroxyphenylalanine is transported by the amino acid transporters rBAT and LAT2 in renal cortex",
abstract = "The intrarenal autocrine-paracrine dopamine (DA) system is critical for Na+ homeostasis. L-Dihydroxyphenylalanine (L-DOPA) uptake from the glomerular filtrate and plasma provides the substrate for DA generation by the renal proximal tubule. The transporter(s) responsible for proximal tubule L-DOPA uptake has not been characterized. Renal cortical poly-A+ RNA injected into Xenopus laevis oocytes induced L-DOPA uptake in a time- and dose-dependent fashion with biphasic kms in the millimolar and micromolar range and independent of inward Na+, K+, of H+ gradients, suggesting the presence of low- and high-affinity L-DOPA carriers. Complementary RNA from two amino acid transporters yielded L-DOPA uptake significantly above water-injected controls the rBATP o.+ AT dimer (rBAT) and the LAT2/4F2 dimer (LAT2). In contradistinction to renal cortical poly-A+, L-DOPA kinetics of rBAT and LAT2 showed classic Michaelis-Menton kinetics with Kms in the micromolar and millimolar range, respectively. Sequence-specific antisense oligonucleotides to rBAT or LAT2 (AS) caused inhibition of rBAT and LAT2 cRNA-induced L-DOPA transport and cortical poly-A+-induced arginine and phenylalanine transport. However, the same ASs only partially blocked poly-A+-induced L-DOPA transport. In cultured kidney cells, silencing inhibitory RNA (siRNA) to rBAT significantly inhibited L-DOPA uptake. We conclude that rBAT and LAT2 can mediate apical and basolateral L-DOPA uptake into the proximal tubule, respectively. Additional L-DOPA transport mechanisms exist in the renal cortex that remain to be identified.",
keywords = "Amino acid transport, Proximal tubule, Sodium balance",
author = "Henry Qui{\~n}ones and Roberto Collazo and Moe, {Orson W.}",
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TY - JOUR

T1 - The dopamine precursor L-dihydroxyphenylalanine is transported by the amino acid transporters rBAT and LAT2 in renal cortex

AU - Quiñones, Henry

AU - Collazo, Roberto

AU - Moe, Orson W.

PY - 2004/7

Y1 - 2004/7

N2 - The intrarenal autocrine-paracrine dopamine (DA) system is critical for Na+ homeostasis. L-Dihydroxyphenylalanine (L-DOPA) uptake from the glomerular filtrate and plasma provides the substrate for DA generation by the renal proximal tubule. The transporter(s) responsible for proximal tubule L-DOPA uptake has not been characterized. Renal cortical poly-A+ RNA injected into Xenopus laevis oocytes induced L-DOPA uptake in a time- and dose-dependent fashion with biphasic kms in the millimolar and micromolar range and independent of inward Na+, K+, of H+ gradients, suggesting the presence of low- and high-affinity L-DOPA carriers. Complementary RNA from two amino acid transporters yielded L-DOPA uptake significantly above water-injected controls the rBATP o.+ AT dimer (rBAT) and the LAT2/4F2 dimer (LAT2). In contradistinction to renal cortical poly-A+, L-DOPA kinetics of rBAT and LAT2 showed classic Michaelis-Menton kinetics with Kms in the micromolar and millimolar range, respectively. Sequence-specific antisense oligonucleotides to rBAT or LAT2 (AS) caused inhibition of rBAT and LAT2 cRNA-induced L-DOPA transport and cortical poly-A+-induced arginine and phenylalanine transport. However, the same ASs only partially blocked poly-A+-induced L-DOPA transport. In cultured kidney cells, silencing inhibitory RNA (siRNA) to rBAT significantly inhibited L-DOPA uptake. We conclude that rBAT and LAT2 can mediate apical and basolateral L-DOPA uptake into the proximal tubule, respectively. Additional L-DOPA transport mechanisms exist in the renal cortex that remain to be identified.

AB - The intrarenal autocrine-paracrine dopamine (DA) system is critical for Na+ homeostasis. L-Dihydroxyphenylalanine (L-DOPA) uptake from the glomerular filtrate and plasma provides the substrate for DA generation by the renal proximal tubule. The transporter(s) responsible for proximal tubule L-DOPA uptake has not been characterized. Renal cortical poly-A+ RNA injected into Xenopus laevis oocytes induced L-DOPA uptake in a time- and dose-dependent fashion with biphasic kms in the millimolar and micromolar range and independent of inward Na+, K+, of H+ gradients, suggesting the presence of low- and high-affinity L-DOPA carriers. Complementary RNA from two amino acid transporters yielded L-DOPA uptake significantly above water-injected controls the rBATP o.+ AT dimer (rBAT) and the LAT2/4F2 dimer (LAT2). In contradistinction to renal cortical poly-A+, L-DOPA kinetics of rBAT and LAT2 showed classic Michaelis-Menton kinetics with Kms in the micromolar and millimolar range, respectively. Sequence-specific antisense oligonucleotides to rBAT or LAT2 (AS) caused inhibition of rBAT and LAT2 cRNA-induced L-DOPA transport and cortical poly-A+-induced arginine and phenylalanine transport. However, the same ASs only partially blocked poly-A+-induced L-DOPA transport. In cultured kidney cells, silencing inhibitory RNA (siRNA) to rBAT significantly inhibited L-DOPA uptake. We conclude that rBAT and LAT2 can mediate apical and basolateral L-DOPA uptake into the proximal tubule, respectively. Additional L-DOPA transport mechanisms exist in the renal cortex that remain to be identified.

KW - Amino acid transport

KW - Proximal tubule

KW - Sodium balance

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U2 - 10.1152/ajprenal.00237.2003

DO - 10.1152/ajprenal.00237.2003

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JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

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