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

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+, 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/b0,+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 antise...