Hama H, Sakurai T, Kasuya Y, Fujiki M, Masaki T, Goto K
Department of Environmental Medicine, University of Tsukuba, Ibaraki, Japan.
Biochem Biophys Res Commun. 1992 Jul 15;186(1):355-62. doi: 10.1016/s0006-291x(05)80815-0.
We investigated the effect of ET-1 on the state of rat cerebral astrocytes (AC) differentiation. AC ceased to proliferate and changed into its differentiated state by treatment with dibutyryl cyclic AMP (DBcAMP). The cell growth activity in DBcAMP-treated AC was stimulated by ET-1 in a dose-dependent manner. Over similar dose ranges, ET-1 suppressed the glutamine synthetase activity in DBcAMP-treated AC. The molar potency of ET-1 in this action was at least 3 orders of magnitude higher than that in mitogenic action in AC under the proliferative state previously reported. Northern blot analysis revealed that ETB receptor mRNA level in DBcAMP-treated AC was markedly higher than that in AC untreated with DBcAMP. Consistently, binding studies showed that the Bmax value for [125I]ET-1 in DBcAMP-treated AC was 16 times higher than that in AC untreated with DBcAMP. These results suggest that ET-1 potently induced a retraction of the differentiation state of AC from fully the specialized state and that the high responsiveness of differentiated AC to ET-1 was partly attributed to the high level expression of the ETB receptor.
我们研究了内皮素-1（ET-1）对大鼠脑星形胶质细胞（AC）分化状态的影响。通过用二丁酰环磷腺苷（DBcAMP）处理，AC停止增殖并转变为分化状态。ET-1以剂量依赖性方式刺激经DBcAMP处理的AC中的细胞生长活性。在相似的剂量范围内，ET-1抑制经DBcAMP处理的AC中的谷氨酰胺合成酶活性。ET-1在此作用中的摩尔效力比先前报道的增殖状态下AC的促有丝分裂作用中的效力至少高3个数量级。Northern印迹分析显示，经DBcAMP处理的AC中ETB受体mRNA水平明显高于未用DBcAMP处理的AC。一致地，结合研究表明，经DBcAMP处理的AC中[125I]ET-1的Bmax值比未用DBcAMP处理的AC高16倍。这些结果表明，ET-1有力地诱导AC的分化状态从完全特化状态回缩，并且分化的AC对ET-1的高反应性部分归因于ETB受体的高水平表达。
