Estrogen mediated inhibition of dopamine transport in the striatum: regulation by G alpha i/o.
Estrogen mediated inhibition of dopamine transport in the striatum: regulation by G alpha i/o.
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雌激素介导的纹状体多巴胺转运抑制：G α i/o 的调节。
DOI：
10.1016/j.ejphar.2005.02.005
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Certain,MatthewE
中科院分区：
文献类型：
--
作者：
Thompson,TinaL;Certain,MatthewE
在本研究中，雌激素启动和多巴胺D2受体激活对多巴胺摄取的卵巢切除雌性大鼠纹状体之间的相互作用进行了研究。在去卵巢、雌激素预处理或N-p-（异硫氰酸苯乙基）螺哌隆（NIPS）处理的大鼠制备的突触体膜中检测了Gi/o的基础ADP-[32 Pi]核糖基化。[32 Pi]-掺入在NIPS处理的动物的组织中显著增加（141%），但在雌激素致敏的动物的组织中减弱（57%）。在通过百日咳毒素（0.5 μg，48 h）操作异源三聚体G蛋白后，在体内测量多巴胺摄取动力学。百日咳毒素显着抑制多巴胺摄取在所有浓度的多巴胺检查。与雌激素和百日咳毒素的共同治疗导致多巴胺转运在高，但不是低浓度的进一步衰减。这些数据与雌激素介导的G蛋白活性改变一致，并支持雌激素可能通过调节多巴胺D2自身受体/Gαi/o蛋白偶联来改变转运蛋白活性的假设。
In the current study, the interaction between estrogen priming and dopamine D2 receptor activation on dopamine uptake in the striatum of ovariectomized female rats was investigated. Basal ADP-[32Pi]ribosylation of Gi/owas examined in synaptosomal membranes prepared from ovariectomized, estrogen primed or N-p-(isothiocyanatophenethyl) spiperone (NIPS) treated rats. [32Pi]-incorporation was significantly increased (141%) in tissue from NIPS treated animals but attenuated (57%) in tissue from estrogen primed animals. Dopamine uptake kinetics were measured in vivo following manipulation of the heterotrimeric G-protein by pertussis toxin (0.5 μg, 48 h). Pertussis toxin significantly inhibited dopamine uptake at all concentrations of dopamine examined. Co-treatment with estrogen and pertussis toxin resulted in a further attenuation of dopamine transport at high but not low dopamine concentrations. These data are consistent with an estrogen mediated alteration of G-protein activity and support the hypothesis that estrogen may alter transporter activity through a modulation of dopamine D2 autoreceptor/Gαi/oprotein coupling.