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

被引:512
作者
MACCUMBER, MW
ROSS, CA
SNYDER, SH
机构
[1] JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, 725 N WOLFE ST, BALTIMORE, MD 21205 USA
[2] JOHNS HOPKINS UNIV, SCH MED, DEPT MOLEC BIOL, BALTIMORE, MD 21205 USA
[3] JOHNS HOPKINS UNIV, SCH MED, DEPT OPHTHALMOL, BALTIMORE, MD 21205 USA
[4] JOHNS HOPKINS UNIV, SCH MED, DEPT PHARMACOL, BALTIMORE, MD 21205 USA
[5] JOHNS HOPKINS UNIV, SCH MED, DEPT PSYCHIAT & BEHAV SCI, BALTIMORE, MD 21205 USA
关键词
Cerebellum; Inositolphospholipid turnover; Peptide; Receptor binding sites; Trophic factor; Vasoconstrictor;
D O I
10.1073/pnas.87.6.2359
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:2359 / 2363
页数:5
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