Meloni R, Gale K
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA.
Neuroreport. 1995 Mar 7;6(4):666-8. doi: 10.1097/00001756-199503000-00020.
Release of dopamine (DA) from the terminals of solid fetal mesencephalic grafts has been shown to be modulated by DA receptor activity. In order to determine whether DA synthesis in the terminals of these grafts is regulated by the host, we examined the activity of tyrosine hydroxylase (TH), the rate limiting enzyme in the synthesis of dopamine, after blockade of DA receptors with haloperidol (HAL). Solid fetal mesencephalic tissue was grafted over the dorsal surface of the striatum, ipsilateral to a 6-hydroxydopamine lesion in the medial forebrain bundle. Systemic administration of HAL caused an activation of TH in the transplant terminals, reflected by an increased affinity of TH for the pteridine cofactor. Our results indicate that a transneuronal feedback mechanism similar to that operating in the intact nigrostriatal system is regulating DA synthesis and utilization in the terminals of the transplant.
已表明,来自实体胎儿中脑移植物终末的多巴胺(DA)释放受DA受体活性调节。为了确定这些移植物终末中的DA合成是否受宿主调节,我们在用氟哌啶醇(HAL)阻断DA受体后,检测了酪氨酸羟化酶(TH)的活性,TH是多巴胺合成中的限速酶。将实体胎儿中脑组织移植到纹状体背表面,与内侧前脑束中6-羟基多巴胺损伤同侧。全身给予HAL导致移植终末中TH的激活,表现为TH对蝶啶辅因子的亲和力增加。我们的结果表明,一种类似于完整黑质纹状体系统中起作用的跨神经元反馈机制正在调节移植物终末中的DA合成和利用。