ENDOTHELIN IN BRAIN - RECEPTORS, MITOGENESIS, AND BIOSYNTHESIS IN GLIAL-CELLS

ENDOTHELIN IN BRAIN - RECEPTORS, MITOGENESIS, AND BIOSYNTHESIS IN GLIAL-CELLS
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DOI:
10.1073/pnas.87.6.2359
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发表时间:
1990-03-01
影响因子:
11.1
通讯作者:
SNYDER, SH
SNYDER, SH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
MACCUMBER, MW;ROSS, CA;SNYDER, SH

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我们已经探索了内皮素(ET)的行动和形成在大脑中的细胞位点,使用小脑突变小鼠以及原代和连续细胞培养。神经胶质细胞的作用是有利的几个观察:(i)突变小鼠缺乏神经元浦肯野细胞显示正常的ET受体结合和增强的肌醇磷脂周转的ET刺激;(ii)在韦弗小鼠缺乏神经元颗粒细胞,肌醇磷脂周转的ET刺激没有显着减少;(iii)C6神经胶质瘤细胞和小脑星形胶质细胞的原代培养物表现出大量的ET受体结合和ET诱导的肌醇磷脂更新刺激;(iv)ET促进C6胶质瘤细胞和原代小脑星形胶质细胞的有丝分裂;和(v)小脑星形胶质细胞的原代培养物含有ET mRNA。ET似乎也有神经元的作用,因为它刺激肌醇磷脂周转小脑颗粒细胞的原代培养物,和ET结合颗粒细胞缺陷小鼠下降。因此,ET可以由胶质细胞产生,并以旁分泌方式作用于胶质细胞和神经元。
We have explored the cellular loci of endothelin (ET) actions and formation in the brain, using cerebellar mutant mice as well as primary and continuous cell cultures. A glial role is favored by several observations: (i) mutant mice lacking neuronal Purkinje cells display normal ET receptor binding and enhanced stimulation by ET of inositolphospholipid turnover; (ii) in weaver mice lacking neuronal granule cells, ET stimulation of inositolphospholipid turnover is not significantly diminished; (iii) C6 glioma cells and primary cultures of cerebellar astroglia exhibit substantial ET receptor binding and ET-induced stimulation of inositolphospholipid turnover; (iv) ET promotes mitogenesis of C6 glioma cells and primary cerebellar astroglia; and (v) primary cultures of cerebellar astroglia contain ET mRNA. ET also appears to have a neuronal role, since it stimulates inositolphospholipid turnover in primary cultures of cerebellar granule cells, and ET binding declines in granule cell-deficient mice. Thus, ET can be produced by glia and act upon both glia and neurons in a paracrine fashion.