Endothelin-1 Activates Mitogen-Activated Protein Kinases Through Two Independent Signaling Pathways in Rat Astrocytes

Y. Kasuya, Yoichiro Abe, H. Hama, T. Sakurai, S. Asada, T. Masaki, K. Goto

研究成果: Article

47 引用 (Scopus)


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.

ジャーナルBiochemical and Biophysical Research Communications
出版物ステータスPublished - 1994 11 14


ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry