Native human neocortex release-regulating dopamine D2 type autoreceptors are dopamine D2 subtype
Native human neocortex release-regulating dopamine D2 type autoreceptors are dopamine D2 subtype
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DOI：
10.1046/j.1460-9568.1999.00651.x
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发表时间：
1999-07-01
影响因子：
3.4
通讯作者：
Raiteri, M
中科院分区：
文献类型：
--
作者：
Fedele, E;Fontana, G;Raiteri, M
多巴胺（DA）神经末梢表达的DA自身受体调节DA的释放。相当多的证据表明，在啮齿动物中，这些自身受体属于DA受体家族的D2型，而DA受体家族又包括D-2、D-3和D-4亚型。我们在这里调查，第一次，本地人类DA自身受体的亚类，通过研究释放的[H-3]DA诱发的电刺激新鲜的人类新皮层切片。结果进行了比较，在三个动物系统：大鼠新皮层和纹状体切片和大鼠中脑神经元培养。在人类新皮层切片中，D-2/D-3受体激动剂喹吡罗（1 nM-10 μ M）抑制氚释放，计算的EC 50为17 nM，在1 μ M时达到约75%的最大抑制。在D-2/D-3受体拮抗剂（-）-舒必利存在下（0.1和1 μ M）时，喹吡罗的浓度-反应曲线右移，表观pA（2）平均值为8.5（8.14-8.77）;另一方面，喹吡罗的抑制作用不受D-3受体选择性拮抗剂[7-N，N-二丙基氨基-5，6，7，8-四氢-萘并（2，3 B）二氢，2，3-呋喃]（S 14297）和D-4受体选择性拮抗剂3-（4-[4-氯苯基]哌嗪-1-基）-甲基-1H-吡咯并[2，3-B]吡啶（L-745，870）（每种情况下0.01-1 μ M）。重叠的结果时，已获得释放引起的大鼠纹状体切片或多巴胺中脑神经元的文化，而出现在大鼠皮质切片的情况下，定量差异。结论：在人脑和大鼠脑中，中脑多巴胺能神经元终末区DA的释放是通过D-2亚型自身受体调节的。
Dopamine (DA) autoreceptors expressed at DA nerve terminals regulate DA release. Considerable evidence has indicated that, in rodents, these autoreceptors belong to the D2 type of the DA receptor family, which, in turn, comprises the D-2, D-3 and D-4 subtypes. We investigated here, for the first time, the subclassification of native human DA autoreceptors by studying the release of [H-3]DA evoked by electrical stimulation in fresh human neocortical slices. The results have been compared with those obtained in three animal systems: rat neocortical and striatal slices and rat mesencephalic neuronal cultures. In human neocortical slices, the D-2/D-3 receptor agonist quinpirole (1 nM-10 mu M) inhibited tritium release with a calculated EC50 of 17 nM and a maximal inhibition of approximate to 75% reached at 1 mu M. In the presence of the D-2/D-3 receptor antagonist (-)-sulpiride (0.1 and 1 mu M), the concentration-response curve of quinpirole was shifted to the right, and the apparent pA(2) mean value was 8.5 (8.14-8.77); on the other hand, the inhibitory effects of quinpirole were not affected by the D-3 receptor-selective antagonist [7-N,N-dipropylamino-5,6,7,8-tetrahydro-naphtho(2,3b) dihydro,2,3-furane] (S 14297) and the D-4 receptor-selective antagonist 3-(4-[4-chlorophenyl]piperazin-1-yl)-methyl-1H-pyrrolo [2,3-b]pyridine (L-745,870) (0.01-1 mu M in each case). Superimposable results have been obtained when the release was elicited from rat striatal slices or dopamine mesencephalic neurons in culture, whereas quantitative differences emerged in the case of rat cortical slices. It is concluded that in human brain, as well as in rat brain, the release of DA in the terminal region of midbrain dopaminergic neurons is regulated through autoreceptors of the D-2 subtype.