Castel M N, Malgouris C, Blanchard J C, Laduron P M
Rhône-Poulenc Santé, Centre de Recherches de Vitry-Alfortville, Vitry-sur-Seine, France.
Neuroscience. 1990;36(2):425-30. doi: 10.1016/0306-4522(90)90438-a.
Although the existence of receptor transport has been clearly demonstrated in peripheral nerves, there is no clear cut evidence in the brain of such a process for neuropeptide receptors. Because of the localization of neurotensin receptors on dopaminergic terminals, the dopaminergic nigrostriatal pathway appears to be the system of choice for studying the axonal transport of neuropeptide receptors in the brain. When labelled neurotensin was injected into the rat striatum, a delayed accumulation of radioactivity in the ipsilateral substantia nigra was observed about 2 h after injection. An essential requirement to clearly observe this phenomenon was the pretreatment of animals with kelatorphan in order to prevent the labelled neurotensin degradation. The appearance of this labelling was prevented by injection of an excess of unlabelled neurotensin or of neurotensin 8-13, an active neurotensin fragment, but not by neurotensin 1-8, which had no affinity for neurotensin receptors. This process was saturable, microtubule-dependent and occurred only in mesostriatal and nigrostriatal dopaminergic neurons as identified after 6-hydroxydopamine lesion and by autoradiography. These results demonstrate that neurotensin was retrogradely transported by a process involving neurotensin receptors. The retrograde transport of receptor-bound neuropeptide may represent an important dynamic process which conveys information molecules from the synapse towards the cell body.
虽然受体运输的存在已在外周神经中得到明确证实，但在大脑中对于神经肽受体而言，尚无此类过程的确凿证据。由于神经降压素受体定位于多巴胺能终末，多巴胺能黑质纹状体通路似乎是研究大脑中神经肽受体轴突运输的理想系统。当将标记的神经降压素注入大鼠纹状体时，注射后约2小时观察到同侧黑质中放射性的延迟积累。清晰观察到这一现象的一个必要条件是用凯他orphan对动物进行预处理，以防止标记的神经降压素降解。通过注射过量的未标记神经降压素或神经降压素8 - 13（一种活性神经降压素片段）可阻止这种标记的出现，但对神经降压素受体无亲和力的神经降压素1 - 8则不能。这个过程是可饱和的、依赖微管的，并且仅发生在经6 - 羟基多巴胺损伤后通过放射自显影鉴定的中脑纹状体和黑质纹状体多巴胺能神经元中。这些结果表明，神经降压素通过涉及神经降压素受体的过程进行逆向运输。受体结合的神经肽的逆向运输可能代表了一个重要的动态过程，该过程将信息分子从突触传向细胞体。
