Effects of several cations on the neuronal uptake of dopamine and the specific binding of [3H]GBR 12783: attempts to characterize the Na+ dependence of the neuronal transport of dopamine

J Neurochem. 1992 Nov;59(5):1795-804. doi: 10.1111/j.1471-4159.1992.tb11012.x.


We have studied the effects of several cations on (1) the neuronal uptake of [3H]dopamine ([3H]DA) and (2) the specific binding of 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl-2-[1-3H]propenyl)piperazi ne ([3H]GBR 12783) to a site associated with the neuronal carrier of DA, in preparations obtained from rat striatum. When studied under the same experimental conditions, both the uptake of [3H]DA and the binding of [3H]GBR 12783 were similarly impaired by the gradual replacement of NaCl by sucrose. In both processes, no convenient substitute for Na+ was found. Furthermore, potential substitutes of Na+ acted as inhibitors of the uptake with a rank order of potency as follows: K+ = Li+ > or = Cs+ > or = Rb+ > choline+ > Tris+ > sucrose, which was somewhat different from that observed in binding studies, i.e., Cs+ > Rb+ > choline+ > or = K+ > Li+ > Tris+ > sucrose. In the presence of either 36 mM or 136 mM Na+, [3H]DA uptake was optimal with 2 mM Mg2+, 1 mM K+, or 1 mM Ca2+. In contrast, higher concentrations of divalent cations competitively blocked the uptake process. K+ concentrations > 50 mM impaired the specific binding, whereas in the millimolar range of concentrations, K+ noncompetitively inhibited the uptake. Decreasing the Na+ concentration increased the inhibitory effect of K+, Ca2+, and Mg2+ on the specific uptake. An increase in NaCl concentration from 0 to 120 mM elicited a significant decline in the affinity of some substrates for the [3H]GBR 12783 binding site. An uptake study performed using optimal experimental conditions defined in the present study revealed that decreasing Na+ concentration reduces the affinity of DA for the neuronal transport. We propose a hypothetical model for the neuronal transport of DA in which both Na+ and K+ membrane gradients are involved.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Biological Transport / drug effects
  • Calcium / pharmacology
  • Dopamine / pharmacokinetics*
  • Dopamine Antagonists
  • Dose-Response Relationship, Drug
  • Magnesium / pharmacology
  • Male
  • Metals / pharmacology*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Piperazines / pharmacokinetics*
  • Potassium / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Chloride / pharmacology


  • Dopamine Antagonists
  • Metals
  • Piperazines
  • Sodium Chloride
  • 1-(2-(diphenylmethoxy)ethyl)-4-(3-phenyl-2-propenyl)piperazine
  • Magnesium
  • Potassium
  • Calcium
  • Dopamine