Hayashi H, Hirota S, Takeo S
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1, Horinouchi, Hachioji, Tokyo 192-03, Japan.
Brain Res. 1998 Oct 19;808(2):190-6. doi: 10.1016/s0006-8993(98)00827-0.
The present study was undertaken to elucidate pathophysiological changes in noradrenaline (NA) transporter and Na+/K+-ATPase, key regulators of cation gradient across the plasma membrane, in nerve terminals of the cerebral cortex after microsphere-induced cerebral embolism in rats. The Vmax value of NA uptake, when analyzed by the Eadie-Hofstee plot, tended to decrease on the 1st day and decreased on the 3rd and 7th days after the embolism without any change in the Km value. The NA content in cerebrocortical synaptosomes did not alter on the 1st day, but decreased on the 3rd and 7th days after the embolism. Ouabain (1 mM) inhibited NA uptake on the 1st day, but did not alter the uptake on the 3rd and 7th days after the embolism. The activity of Na+/K+-ATPase of cerebrocortical synaptosomes increased on the 1st day and gradually decreased up to the 7th day after the embolim. These results suggest that NA uptake in nerve terminals of the cerebral cortex decreased after microsphere embolism, which may be due to a reduction in function of NA transporters. The changes in Na+/K+-ATPase following microsphere embolism may represent a compensatory action to maintain ion homeostasis in nerve terminals at an early stage of ischemic injury.
本研究旨在阐明大鼠微球诱导脑栓塞后,大脑皮质神经末梢中去甲肾上腺素(NA)转运体和Na+/K+-ATP酶(跨质膜阳离子梯度的关键调节因子)的病理生理变化。用伊迪-霍夫斯蒂图分析时,栓塞后第1天NA摄取的Vmax值呈下降趋势,第3天和第7天下降,而Km值无变化。脑皮质突触体中的NA含量在栓塞后第1天无变化,但在第3天和第7天下降。哇巴因(1 mM)在栓塞后第1天抑制NA摄取,但在第3天和第7天不改变摄取。脑皮质突触体的Na+/K+-ATP酶活性在栓塞后第1天增加,并在第7天前逐渐下降。这些结果表明,微球栓塞后大脑皮质神经末梢的NA摄取减少,这可能是由于NA转运体功能降低所致。微球栓塞后Na+/K+-ATP酶的变化可能代表缺血损伤早期维持神经末梢离子稳态的一种代偿作用。