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Effects of Several Cations on the Neuronal Uptake of Dopamine and the Specific Binding of [ 3 H]GBR 12783: Attempts to Characterize the Na + Dependence of the Neuronal Transport of Dopamine
Author(s) -
AmejdkiChab N.,
Benmansour S.,
Costentin J.,
Bonnet J.J.
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb11012.x
Subject(s) - chemistry , divalent , dopamine , striatum , sucrose , choline , stereochemistry , molar concentration , biochemistry , biophysics , endocrinology , biology , organic chemistry
We have studied the effects of several cations on (1) the neuronal uptake of [ 3 H]dopamine ([ 3 H]DA) and (2) the specific binding of 1‐[2‐(diphenylmethoxy)ethyl]‐4‐(3‐phenyl‐2‐[1‐ 3 H]propenyl)piperazine ([ 3 H]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 [ 3 H]DA and the binding of [ 3 H]GBR 12783 were similarly impaired by the gradual replacement of NaCl by sucrose. In both processes, no convenient substitute for N a+ 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 + , [ 3 H]DA uptake was optimal with 2 mM Mg 2+ , 1 mM K + , or 1 mM Ca 2+ . 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 + , Ca 2+ , and Mg 2+ 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 [ 3 H]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.