PMID- 15180924
OWN - NLM
STAT- MEDLINE
DCOM- 20040708
LR  - 20171116
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 287
IP  - 1
DP  - 2004 Jul
TI  - The dopamine precursor L-dihydroxyphenylalanine is transported by the amino acid 
      transporters rBAT and LAT2 in renal cortex.
PG  - F74-80
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 K(m)s in the millimolar and micromolar range and independent of inward 
      Na(+), K(+), or 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 rBAT/b(0,+)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 K(m)s 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.
FAU - Quinones, Henry
AU  - Quinones H
AD  - Department of Internal Medicine, University of Texas Southwestern Medical Center, 
      Dallas, TX 75390-8856, USA. henry.quinones@utsouthwestern.edu
FAU - Collazo, Roberto
AU  - Collazo R
FAU - Moe, Orson W
AU  - Moe OW
LA  - eng
GR  - R01-DK-48482/DK/NIDDK NIH HHS/United States
GR  - R01-DK-54392/DK/NIDDK NIH HHS/United States
GR  - T32 DK-07257-17/DK/NIDDK NIH HHS/United States
GR  - T32 DK-07257-2031/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Amino Acid Transport System y+)
RN  - 0 (Amino Acid Transport Systems, Basic)
RN  - 0 (Amino Acids)
RN  - 0 (Carrier Proteins)
RN  - 0 (Dopamine Agents)
RN  - 0 (Fusion Regulatory Protein 1, Light Chains)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Slc7a8 protein, rat)
RN  - 46627O600J (Levodopa)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Amino Acid Transport System y+/*pharmacology
MH  - *Amino Acid Transport Systems, Basic
MH  - Amino Acids/*pharmacokinetics
MH  - Animals
MH  - Carrier Proteins/*pharmacology
MH  - Cell Culture Techniques
MH  - Dopamine Agents/*pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Fusion Regulatory Protein 1, Light Chains/*pharmacology
MH  - Kidney Cortex/*physiology
MH  - Levodopa/*pharmacokinetics
MH  - Membrane Glycoproteins/*pharmacology
MH  - Oocytes/physiology
MH  - RNA
MH  - RNA Interference
MH  - Rats
MH  - Xenopus laevis/physiology
EDAT- 2004/06/08 05:00
MHDA- 2004/07/09 05:00
CRDT- 2004/06/08 05:00
PHST- 2004/06/08 05:00 [pubmed]
PHST- 2004/07/09 05:00 [medline]
PHST- 2004/06/08 05:00 [entrez]
AID - 287/1/F74 [pii]
AID - 10.1152/ajprenal.00237.2003 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2004 Jul;287(1):F74-80. doi: 
      10.1152/ajprenal.00237.2003.