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Cell inward transport of l ‐DOPA and 3‐O‐methyl‐ l ‐DOPA in rat renal tubules
Author(s) -
SoaresdaSilva P.,
Fernandes M.H.,
PintodoOA P.C.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13118.x
Subject(s) - aromatic l amino acid decarboxylase , chemistry , dopamine , kinetics , kidney , dihydroxyphenylalanine , endocrinology , medicine , biology , physics , quantum mechanics
1 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. 2 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, V max = 11.1 nmol mg −1 protein h −1 and K m = 216 μ m ( n = 6); 3‐OMDOPA, V max = 8.1 nmol mg −1 protein h −1 and K m = 231 μ m ( 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 3‐OMDOPA (100 to 2000 μ m ) was found to produce a concentration‐dependent decrease (29% to 81% reduction) of the saturable component of the tubular uptake of l ‐DOPA; the K i value of 3‐OMDOPA for inhibition of l ‐DOPA uptake was found to be 181 μ m ( n = 5). The accumulation of l ‐DOPA obtained in experiments conducted at 4°C was not affected by 3‐OMDOPA. 4 In experiments conducted in kidney homogenates only l ‐DOPA (10 to 5000 μ m ) was found to be decarboxylated. The V max and K m values for aromatic l ‐amino acid decarboxylase determined in the absence of 3‐OMDOPA ( V max = 14.1 nmol mg −1 protein h −1 ; K m = 62 μ m ) were not significantly different from those observed when the decarboxylation of l ‐DOPA was carried out in the presence of 1000 μ m 3‐OMDOPA ( V max = 15.7 nmol mg −1 protein h −1 ; K m = 68 μ m ). 5 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.