title: Kinetic study of the tubular dopamine outward transporter in the rat and dog kidney.
abstract: 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 microM). 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 microM 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 Vmax (nmol g-1 15 min-1) and Km (nM) 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.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
authors.forename: P
authors.initials: P
authors.lastname: Soares-da-Silva
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004285:Dogs; D004298:Dopamine / Q000493:pharmacokinetics*; D050483:Dopamine Plasma Membrane Transport Proteins; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000378:metabolism*; D007980:Levodopa / Q000493:pharmacokinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
chemical_list: D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D007980:Levodopa; D004298:Dopamine