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Kinetic study of the tubular dopamine outward transporter in the rat and dog kidney
Author(s) -
SoaresdaSilva P.
Publication year - 1993
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.1476-5381.1993.tb13609.x
Subject(s) - dopamine , kidney , endocrinology , chemistry , medicine , renal cortex , incubation , decarboxylation , biology , biochemistry , catalysis
1 The present study has determined the kinetic characteristics of the outflow of dopamine of renal origin in slices of rat and dog renal cortex loaded with exogenous l ‐dihydroxyphenylalanine ( l ‐DOPA 5 to 5000 μ m ). 2 In both dog and rat renal tissues the production of dopamine was found to be dependent on the concentration of l ‐DOPA used and reached its maximum at 2500 μ m l ‐DOPA. The decarboxylation of l ‐DOPA in rat cortical slices (16.4 ± 2.6 to 1479.2 ± 85.2 nmol g −1 ) was 6 fold that in the dog (2.2 ± 0.4 to 252.1 ± 21.2 nmol g −1 ). In the rat kidney a large amount (approximately 50%) of the dopamine (5.2 ± 0.6 to 743.4 ± 58.3 nmol g −1 ) was found to escape into the incubation medium, whereas in dog renal slices the amount of newly‐formed dopamine escaping into the incubation medium (0.7 ± 0.2 to 46.5 ± 9.3 nmol g −1 ) was less than 25% of the total amount of the amine formed. 3 The application of the Michaelis‐Menten equation to the net transport of newly‐formed dopamine has allowed the identification of a saturable (carrier‐mediated transfer) and a non‐saturable component (diffusion). The V max (nmol g −1 15 min −1 ) and K m (n m ) values for the saturable component were, respectively, 340 ± 41 and 396 ± 45 in the rat kidney and 112 ± 16 and 319 ± 35 in the dog kidney. In both rat and dog renal tissues, the magnitude of the non‐saturable component was found to be of minor importance up to a concentration of 250 nmol g −1 of dopamine to be transported. At high concentrations of the amine (greater then 250 nmol g −1 ), only attainable in rat kidney slices, most of the dopamine was found to leave the compartment where the synthesis did occur through a non‐saturable transport system. 4 In conclusion, the results presented here show that the outflow of newly‐formed dopamine in both dog and rat kidney slices loaded with exogenous l ‐DOPA follows Michaelis‐Menten kinetics with a saturable component and a non‐saturable one, the latter assuming particular importance only at higher concentrations of the amine.