Disshon K A, Boja J W, Dluzen D E
Department of Anatomy, Northeastern Ohio Universities College of Medicine, Rootstown 44272-0095, USA.
Eur J Pharmacol. 1998 Mar 19;345(2):207-11. doi: 10.1016/s0014-2999(98)00008-9.
Striatal synaptosomes from ovariectomized rats were prepared to examine the effect of 17beta-estradiol on [3H]dopamine uptake. Estradiol inhibited [3H]dopamine uptake in a dose-dependent manner, with an IC50 of 7.2 microM. Use of identical concentrations of progesterone had no effect on [3H]dopamine uptake. The effects of estradiol were exerted by decreasing the affinity of the transporter for dopamine, as revealed by a dose-dependent increase in the Km. The Km values for 0 (control), 10, and 100 microM estradiol were 108+/-11 258+/-44 and 415+/-40 nM, respectively, with each of the three concentrations tested being significantly different among each other. No statistically significant differences were obtained for the Vmax, with values for the three increasing doses being 9.2+/-0.8, 8.3+/-0.5 and 7.3+/-0.8 pmol/min per mg protein. These results demonstrate that estradiol, but not progesterone, inhibits striatal dopamine uptake by decreasing the affinity of the transporter for dopamine. Such a mechanism may serve as one of the bases for the modulatory effects of estradiol upon the nigrostriatal dopaminergic system.
制备去卵巢大鼠的纹状体突触体，以研究17β-雌二醇对[3H]多巴胺摄取的影响。雌二醇以剂量依赖性方式抑制[3H]多巴胺摄取，IC50为7.2微摩尔。使用相同浓度的孕酮对[3H]多巴胺摄取没有影响。雌二醇的作用是通过降低转运体对多巴胺的亲和力来实现的，这表现为Km的剂量依赖性增加。0（对照）、10和100微摩尔雌二醇的Km值分别为108±11、258±44和415±40纳摩尔，所测试的三种浓度中的每一种彼此之间均有显著差异。Vmax没有统计学上的显著差异，三种递增剂量的值分别为每毫克蛋白质9.2±0.8、8.3±0.5和7.3±0.8皮摩尔/分钟。这些结果表明，雌二醇而非孕酮通过降低转运体对多巴胺的亲和力来抑制纹状体多巴胺摄取。这种机制可能是雌二醇对黑质纹状体多巴胺能系统调节作用的基础之一。
