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 journalArticlepeer-review

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

Fingerprint

Dive into the research topics of 'Endothelin-1 activates mitogen-activated protein kinases through two independent signaling pathways in rat astrocytes'. Together they form a unique fingerprint.

Cite this