Nakagomi S, Kiryu-Seo S, Kiyama H
Department of Anatomy, Asahikawa Medical College, Midorigaoka-Higashi, Hokkaido 078-8510, Asahikawa, Japan.
Neuroscience. 2000;101(2):441-9. doi: 10.1016/s0306-4522(00)00345-6.
There is some evidence that endothelins may be a signal mediator between neuronal and glial cells, at least in some regions of the brain. To evaluate this possibility, the localization of messenger RNAs for endothelin-converting enzymes and endothelin receptor B in the rat brain were examined using in situ hybridization histochemistry. The messenger RNAs for endothelin-converting enzyme-1 and endothelin-converting enzyme-2 were expressed mainly in neurons located in various brain regions, whereas the messenger RNA for endothelin receptor B was mainly localized in the astrocytes located throughout the brainstem, Bergmann glia, choroid plexus and ependymal cells. The localization patterns of endothelin-converting enzyme and endothelin receptor B messenger RNAs were strikingly different. For instance, in the cerebellum, endothelin-converting enzyme-1 messenger RNA was localized in Purkinje cells, and endothelin-converting enzyme-2 mRNA was expressed in Purkinje cells and granule cells. On the other hand, endothelin receptor B messenger RNA was expressed in Bergmann glia and the astrocytes located in the granule cell layer. This suggests that final cleavages of big endothelins are performed on neuronal cells, and the major target of the processed endothelins could be astrocytes, which express endothelin receptor B most abundantly in the brain. Since evidence that endothelin is implicated in brain injury has also accumulated, we examined whether the expressions of endothelin-converting enzymes and endothelin receptor B are regulated by nerve injury. Following hypoglossal nerve injury, expression of messenger RNA for endothelin-converting enzymes-1 and -2 and endothelin receptor B was enhanced in the injured motor neurons and astrocytes respectively. The up-regulation of these messenger RNAs was also confirmed by a reverse transcription-polymerase chain reaction based strategyThese results lead us to suggest that endothelin can be an inducible intercellular mediator between injured neurons and astrocytes in response to nerve injury.
有证据表明，内皮素可能是神经元和神经胶质细胞之间的信号介质，至少在大脑的某些区域是这样。为了评估这种可能性，利用原位杂交组织化学技术检测了大鼠脑中内皮素转化酶和内皮素受体B的信使核糖核酸的定位。内皮素转化酶-1和内皮素转化酶-2的信使核糖核酸主要在位于不同脑区的神经元中表达，而内皮素受体B的信使核糖核酸主要定位于遍布脑干的星形胶质细胞、伯格曼胶质细胞、脉络丛和室管膜细胞中。内皮素转化酶和内皮素受体B信使核糖核酸的定位模式明显不同。例如，在小脑中，内皮素转化酶-1信使核糖核酸定位于浦肯野细胞，内皮素转化酶-2信使核糖核酸在浦肯野细胞和颗粒细胞中表达。另一方面，内皮素受体B信使核糖核酸在伯格曼胶质细胞和位于颗粒细胞层的星形胶质细胞中表达。这表明大内皮素的最终裂解在神经元细胞上进行，而加工后的内皮素的主要靶标可能是星形胶质细胞，星形胶质细胞在大脑中最丰富地表达内皮素受体B。由于内皮素与脑损伤有关的证据也在积累，我们研究了内皮素转化酶和内皮素受体B的表达是否受神经损伤的调节。舌下神经损伤后，内皮素转化酶-1和-2以及内皮素受体B的信使核糖核酸表达分别在受损的运动神经元和星形胶质细胞中增强。这些信使核糖核酸的上调也通过基于逆转录-聚合酶链反应的策略得到证实。这些结果使我们认为，内皮素可能是受损神经元和星形胶质细胞之间对神经损伤作出反应的一种可诱导的细胞间介质。
