Cell inward transport of l‐DOPA and 3‐O‐methyl‐l‐DOPA in rat renal tubules

Open Access
Publisher Website
Google Scholar
Abstract
The present study has determined the kinetics of the uptake of l‐3,4‐dihydroxyphenylalanine (l‐DOPA) and 3‐O‐methyl‐l‐DOPA (3‐OMDOPA) in rat renal tubules and examined the effect of 3‐OMDOPA on the inward transport of l‐DOPA and on its conversion into dopamine in kidney homogenates. The accumulation of both l‐DOPA and 3‐OMDOPA in renal tubules was found to occur through non‐saturable and saturable mechanisms. The kinetics of the saturable component of l‐DOPA and 3‐OMDOPA uptake in renal tubules were as follows: l‐DOPA, Vmax = 11.1 nmol mg−1 protein h−1 and Km = 216 μm (n = 6); 3‐OMDOPA, Vmax = 8.1 nmol mg−1 protein h−1 and Km = 231 μm (n = 5). The diffusion constant of the non‐saturable component for the accumulation of l‐DOPA and 3‐OMDOPA was 0.0010 and 0.0014 μmol−1, respectively. 3‐OMDOPA (100 to 2000 μm) was found to produce a concentration‐dependent decrease (29% to 81% reduction) of the saturable component of the tubular uptake of l‐DOPA; the Ki value of 3‐OMDOPA for inhibition of l‐DOPA uptake was found to be 181 μm (n = 5). The accumulation of l‐DOPA obtained in experiments conducted at 4°C was not affected by 3‐OMDOPA. In experiments conducted in kidney homogenates only l‐DOPA (10 to 5000 μm) was found to be decarboxylated. The Vmax and Km values for aromatic l‐amino acid decarboxylase determined in the absence of 3‐OMDOPA (Vmax = 14.1 nmol mg−1 protein h−1; Km = 62 μm) were not significantly different from those observed when the decarboxylation of l‐DOPA was carried out in the presence of 1000 μm 3‐OMDOPA (Vmax = 15.7 nmol mg−1 protein h−1; Km = 68 μm). It is concluded that the tubular uptake of both l‐DOPA and 3‐OMDOPA occur through non‐saturable and saturable mechanisms; only the saturable tubular uptake of l‐DOPA was found to be inhibited by 3‐OMDOPA. It is further shown that 3‐OMDOPA neither undergoes decarboxylation into 3‐MT nor affects the decarboxylation of l‐DOPA.