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

N. Amejdki‐Chab, S. Benmansour, J. Costentin, J. ‐J Bonnet

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Abstract: 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)piperazine ([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+ gtm Cs+ gtm Rb+ > choline+ > Tris+ > sucrose, which was somewhat different from that observed in binding studies, i.e., Cs+ > Rb+ > choline+ gtm 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.

Original languageEnglish (US)
Pages (from-to)1795-1804
Number of pages10
JournalJournal of Neurochemistry
Volume59
Issue number5
DOIs
StatePublished - Nov 1992

Keywords

  • Cation requirements
  • In vitro binding
  • Key Words: Neuronal uptake of dopamine
  • Rat striatum
  • [H]GBR 12783

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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