Molecular identification of guanine-nucleotide-binding regulatory proteins which couple to endothelin receptors

M. Takigawa, T. Sakurai, Y. Kasuya, Yoichiro Abe, T. Masaki, K. Goto

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

The coupling of two endothelin receptor subtypes (ET(A) and ET(B)) to several types of guanine-nucleotide-binding regulatory protein (G protein) was examined. Two subtypes of receptor cDNAs were transfected alone or together with four different G protein α subunit cDNAs in COS-7 cells. In ET, receptor-transfected cells, endothelin-1 (ET-1) activated phosphatidylinositol-specific phospholipase C as measured by the production of phosphatidylinositol 1,4,5-trisposphate [Ins(1,4,5)P3]. ET(B)-receptor-transfected cells also produced Ins(1,4,5)P3 on stimulation by ET-1. The ET-1-induced production of Ins(1,4,5)P3 was markedly higher in Gα(i2) cotransfected or Gα11-cotransfected cells than in cells transfected with each receptor alone. ET-1 also stimulated production of cAMP in ET(A) or ET(B) receptor-transfected cells. The production of cAMP was synergistically amplified by Gα(s) co-transfection with each receptor. In contrast, when Gα(i2), was co-transfected with the ET(A) or ET(B) receptor, ET-1 displayed an inhibitory action on forskolin-stimulated cAMP accumulation. Pertussis-toxin treatment of the Gα(i2)-transfected cells resulted in abolition of the endothelin-induced inhibition of cAMP accumulation. These observations indicate that both ET(A) and ET(B) receptors are able to couple to G(q), G11, G(s) and G(i2), and suggest that endothelin receptors stimulate multiple effecters via several types of G protein simultaneously. The overall effects induced by endothelin may differ in cell types depending on the level of expression of each G-protein subtype in the cell.

Original languageEnglish
Pages (from-to)102-108
Number of pages7
JournalEuropean Journal of Biochemistry
Volume228
Issue number1
DOIs
Publication statusPublished - 1995
Externally publishedYes

Fingerprint

Endothelin Receptors
Guanine Nucleotides
Endothelin-1
GTP-Binding Proteins
Carrier Proteins
Endothelins
Proteins
Complementary DNA
Endothelin B Receptors
Phosphoinositide Phospholipase C
Endothelin A Receptors
Pertussis Toxin
Protein Subunits
Colforsin
Phosphatidylinositols
COS Cells
Transfection

Keywords

  • Endothelin
  • Endothelin receptor subtype A
  • Endothelin receptor subtype B
  • Guanine-nucleotide-binding regulatory protein
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry

Cite this

Molecular identification of guanine-nucleotide-binding regulatory proteins which couple to endothelin receptors. / Takigawa, M.; Sakurai, T.; Kasuya, Y.; Abe, Yoichiro; Masaki, T.; Goto, K.

In: European Journal of Biochemistry, Vol. 228, No. 1, 1995, p. 102-108.

Research output: Contribution to journalArticle

Takigawa, M. ; Sakurai, T. ; Kasuya, Y. ; Abe, Yoichiro ; Masaki, T. ; Goto, K. / Molecular identification of guanine-nucleotide-binding regulatory proteins which couple to endothelin receptors. In: European Journal of Biochemistry. 1995 ; Vol. 228, No. 1. pp. 102-108.
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