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

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1325-1333
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume204
Issue number3
DOIs
Publication statusPublished - 1994 Nov 14
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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