Endothelin-1 activates mitogen-activated protein kinases through two independent signaling pathways in rat astrocytes

Yoshitoshi Kasuya, Yoichiro Abe, Hiroshi Hama, Takeshi Sakurai, Sachie Asada, Tomoh Masaki, Katsutoshi Goto

研究成果: Article査読

47 被引用数 (Scopus)

抄録

Northern blot analysis and displacement study revealed that the endothelin (ET) receptor functionally expressed in rat primary cultured astrocytes is the ETB receptor. Mitogen-activated protein kinases (MAP kinases) in the cells were activated by 10 nM ET-1, a dose that maximally stimulated phosphoinositide hydrolysis. This activation was potently inhibited by pretreatment of the cells with phorbol 12-myristate 13-acetate (PMA) which leads to protein kinase C (PKC) down-regulation and was slightly inhibited by pretreatment with pertussis toxin (PTX). Pretreatment of the cells with PMA plus PTX completely inhibited the ET-1-augmented MAP kinase activity. Activation of MAP kinases was also induced by 0.1 nM ET-1, which hardly stimulated phosphoinositide hydrolysis. This activation was fully inhibited by pretreatment with PTX but insensitive to pretreatment with PMA. ET-1-stimulated production of inositol phosphates was not affected by pretreatment with PTX. These results suggest that activation of MAP kinases secondary to stimulation of the ETB receptor with ET-1 in rat primary cultured astrocytes was mediated through two independent signalling pathways, PKC-dependent pathway and PTX-sensitive G protein-mediated pathway.

本文言語English
ページ(範囲)1325-1333
ページ数9
ジャーナルBiochemical and Biophysical Research Communications
204
3
DOI
出版ステータスPublished - 1994 11 14
外部発表はい

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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