Kinetic study of the tubular dopamine outward transporter in the rat and dog kidney

Br J Pharmacol. 1993 Jun;109(2):577-80. doi: 10.1111/j.1476-5381.1993.tb13609.x.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Dogs
  • Dopamine / pharmacokinetics*
  • Dopamine Plasma Membrane Transport Proteins
  • In Vitro Techniques
  • Kidney Tubules / metabolism*
  • Levodopa / pharmacokinetics
  • Male
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Rats
  • Rats, Wistar
  • Species Specificity

Substances

  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Levodopa
  • Dopamine