Molecular Identification of Guanine‐Nucleotide‐Binding Regulatory Proteins which Couple to Endothelin Receptors

Miho Takigawa, Takeshi Sakurai, Yoshitoshi Kasuya, Yoichiro Abe, Tomoh Masaki, Katsutoshi Goto

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

The coupling of two endothelin receptor subtypes (ETA and ETB) 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 ETA receptor‐transfected cells, endothelin‐1 (ET‐1) activated phosphatidylinositol‐specific phospholipase C as measured by the production of phosphatidylinositol 1,4,5‐trisphosphate [Ins(1,4,5)P3]. ETB‐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 Gαq‐cotransfected or Gα11‐cotransfected cells than in cells transfected with each receptor alone. ET‐1 also stimulated production of cAMP in ETA or ETB receptor‐transfected cells. The production of cAMP was synergistically amplified by Gαs co‐transfection with each receptor. In contrast, when Gαi2 was co‐transfected with the ETA or ETB receptor, ET‐1 displayed an inhibitory action on forskolin‐stimulated cAMP accumulation. Pertussis‐toxin treatment of the Gαi2‐transfected cells resulted in abolition of the endothelin‐induced inhibition of cAMP accumulation. These observations indicate that both ETA and ETB receptors are able to couple to Gq, G11, Gs, and Gi2, and suggest that endothelin receptors stimulate multiple effectors 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 Feb
Externally publishedYes

Keywords

  • Endothelin
  • endothelin receptor subtype A
  • endothelin receptor subtype B
  • guanine‐nucleotide‐binding regulatory protein
  • signal transduction

ASJC Scopus subject areas

  • Biochemistry

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