EFFECTS OF SEVERAL CATIONS ON THE NEURONAL UPTAKE OF DOPAMINE AND THE SPECIFIC BINDING OF [H-3] GBR 12783 - ATTEMPTS TO CHARACTERIZE THE NA+ DEPENDENCE OF THE NEURONAL TRANSPORT OF DOPAMINE
EFFECTS OF SEVERAL CATIONS ON THE NEURONAL UPTAKE OF DOPAMINE AND THE SPECIFIC BINDING OF [H-3] GBR 12783 - ATTEMPTS TO CHARACTERIZE THE NA+ DEPENDENCE OF THE NEURONAL TRANSPORT OF DOPAMINE
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DOI：
10.1111/j.1471-4159.1992.tb11012.x
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发表时间：
1992-11-01
影响因子：
4.7
通讯作者：
BONNET, JJ
中科院分区：
文献类型：
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作者：
AMEJDKICHAB, N;BENMANSOUR, S;BONNET, JJ
我们研究了几种阳离子对(1)神经元摄取[H-3]多巴胺（[H-3]DA）和(2)1-[2-（二苯甲氧基）乙基]-4-（3-苯基-2-[1-H-3]丙烯基）哌嗪（[H-3]GBR 12783）与DA神经元载体相关位点的特异性结合的影响，这些制剂来自大鼠纹状体。在相同的实验条件下，随着NaCl的逐渐取代，[H-3]DA的吸收和[H-3]GBR 12783的结合都受到了类似的损害。在这两种工艺中，都没有找到方便的Na+替代品。此外，Na+的潜在替代品作为摄取抑制剂的效价顺序为：K+ = Li+大于或等于Cs+大于或等于Rb+ >胆碱+ > Tris+ >蔗糖，这与结合研究中观察到的Cs+ > Rb+ >胆碱大于或等于K+ > Li+ > Tris+ >蔗糖有所不同。在36 mM或136 mM Na+存在的情况下，2 mM Mg2+、1 mM K+或1 mM Ca2+对[H-3]DA的吸收效果最佳。相反，较高浓度的二价阳离子竞争性地阻断了摄取过程。K+浓度为bb0 ~ 50mm时，抑制了特异性结合，而在毫摩尔浓度范围内，K+非竞争性地抑制了摄取。降低Na+浓度可增强K+、Ca2+和Mg2+对特定摄取的抑制作用。当NaCl浓度从0增加到120 mM时，一些底物对[H-3]GBR 12783结合位点的亲和力显著下降。在本研究中定义的最佳实验条件下进行的摄取研究表明，Na+浓度的降低降低了DA对神经元运输的亲和力。我们提出了一种假设的DA神经元转运模型，其中Na+和K+膜梯度都参与其中。
We have studied the effects of several cations on (1) the neuronal uptake of [H-3]dopamine ([H-3]DA) and (2) the specific binding of 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl-2-[1-H-3]propenyl)piperazine ([H-3]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 [H-3]DA and the binding of [H-3]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+ greater-than-or-equal-to Cs+ greater-than-or-equal-to Rb+ > choline+ > Tris+ > sucrose, which was somewhat different from that observed in binding studies, i.e., Cs+ > Rb+ > choline' greater-than-or-equal-to K+ > Li+ > Tris+ > sucrose. In the presence of either 36 mM or 136 mM Na+, [H-3]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 [H-3]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.