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自发性高血压大鼠和正常血压的Wistar-Kyoto大鼠尾状核中的多巴胺D1和D2受体

Dopamine D1 and D2 receptors in the caudate nucleus of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats.

作者信息

Linthorst A C, De Jong W, De Boer T, Versteeg D H

机构信息

Department of Medical Pharmacology, Rudolf Magnus Institute, Medical Faculty, University of Utrecht, The Netherlands.

出版信息

Brain Res. 1993 Jan 29;602(1):119-25. doi: 10.1016/0006-8993(93)90250-q.

Abstract

A series of studies was carried out to characterize the binding properties of dopamine D1 and D2 receptors in membrane homogenates of the caudate nucleus of spontaneously hypertensive rats (SHR). Binding in SHR was studied at the age of 4 weeks when the rats were still in the prehypertensive phase, and at the age of 8 weeks, during the phase in which blood pressure is increasing dramatically; age-matched normotensive Wistar-Kyoto rats (WKY) were used as controls. Binding to dopamine D1 receptors was studied using [3H]SCH 23390. Antagonist binding of dopamine D2 receptors was performed with [3H]spiperone. At both ages no differences were found between SHR and WKY in affinity (Kd) or concentration (Bmax) of dopamine D1 and D2 receptors. Binding to the high affinity state of the dopamine D2 receptor was measured using the agonist [3H]N-n-propylnorapomorphine (NPA). No differences in Bmax or Kd were found between SHR and WKY at both ages studied, indicating that the ratio between dopamine D2 receptors in the high and in the low affinity state is not altered in spontaneous hypertension. Although the results do not reveal differences in affinities or concentrations of dopamine D1 or D2 receptors in the caudate nucleus between SHR and WKY, a role in the development of hypertension for the here described lack of receptor up-regulation in connection with our previous observation of lower release of dopamine in the caudate nucleus of SHR, cannot be excluded.

摘要

开展了一系列研究以表征自发性高血压大鼠(SHR)尾状核膜匀浆中多巴胺D1和D2受体的结合特性。在4周龄时(此时大鼠仍处于高血压前期)以及8周龄时(血压急剧上升阶段)对SHR的结合情况进行了研究;将年龄匹配的正常血压Wistar-Kyoto大鼠(WKY)用作对照。使用[3H]SCH 23390研究多巴胺D1受体的结合情况。用[3H]螺哌隆进行多巴胺D2受体的拮抗剂结合实验。在这两个年龄段,SHR和WKY在多巴胺D1和D2受体的亲和力(Kd)或浓度(Bmax)方面均未发现差异。使用激动剂[3H]N-正丙基去甲阿朴吗啡(NPA)测量多巴胺D2受体高亲和力状态的结合情况。在所研究的两个年龄段,SHR和WKY在Bmax或Kd方面均未发现差异,这表明在自发性高血压中,多巴胺D2受体高亲和力状态与低亲和力状态的比例未发生改变。尽管结果未揭示SHR和WKY在尾状核中多巴胺D1或D2受体的亲和力或浓度存在差异,但结合我们之前观察到的SHR尾状核中多巴胺释放较低的情况,不能排除此处所描述的缺乏受体上调在高血压发生过程中的作用。

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