title: 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.
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)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.
authors.affiliation: URA 1170 du CNRS, UFR de Médecine et Pharmacie de Rouen, Saint Etienne du Rouvray, France.
authors.forename: N
authors.initials: N
authors.lastname: Amejdki-Chab
authors.forename: S
authors.initials: S
authors.lastname: Benmansour
authors.forename: J
authors.initials: J
authors.lastname: Costentin
authors.forename: J J
authors.initials: JJ
authors.lastname: Bonnet
mesh_terms: D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D004298:Dopamine / Q000493:pharmacokinetics*; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008670:Metals / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000493:pharmacokinetics*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D018492:Dopamine Antagonists; D008670:Metals; D010879:Piperazines; D012965:Sodium Chloride; C039737:1-(2-(diphenylmethoxy)ethyl)-4-(3-phenyl-2-propenyl)piperazine; D008274:Magnesium; D011188:Potassium; D002118:Calcium; D004298:Dopamine