Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor

Takeshi Sakurai, Masashi Yanagisawa, Yoh Takuwa, Hitoshi Miyazaki, Sadao Kimura, Katsutoshi Goto, Tomoh Masaki

Research output: Contribution to journalArticle

2283 Citations (Scopus)

Abstract

ENDOTHELIN-1 was initially identified as a 21-residue potent vasoconstrictor peptide produced by vascular endothelial cells, but was subsequently found to have many effects on both vascular and non-vascular tissues1,2. The discovery of three isopeptides of the endothelin family3, ET-1, ET-2 and ET-3, each possessing a diverse set of pharmacological activities of different potency, suggested the existence of several different endothelin receptor subtypes3-7. Endothelins may elicit biological responses by various signal-transduction mechanisms, including the G protein-coupled activation of phospholipase C and the activation of voltage-dependent Ca2+ channels8-10. Thus, different subtypes of the endothelin receptor may use different signal-transduction mechanisms. Here we report the cloning of a complementary DNA encoding one subtype belonging to the superfamily of G protein-coupled receptors. COS-7 cells transfected with the cDNA express specific and high-affinity binding sites for endothelins, responding to binding by the production of inositol phosphates and a transient increase in the concentration of intracellular free Ca2+. The three endothelin isopeptides are roughly equipotent in displacing 125I-labelled ET-1 binding and causing Ca2+ mobilization. A messenger RNA corresponding to the cDNA is detected in many rat tissues including the brain, kidney and lung but not in vascular smooth muscle cells. These results indicate that this cDNA encodes a 'nonselective' subtype of the receptor which is different from the vascular smooth muscle receptor.

Original languageEnglish (US)
Pages (from-to)732-735
Number of pages4
JournalNature
Volume348
Issue number6303
StatePublished - Dec 20 1990

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Endothelin Receptors
Endothelins
Organism Cloning
Complementary DNA
Vascular Smooth Muscle
Signal Transduction
Inositol Phosphates
COS Cells
Type C Phospholipases
Vasoconstrictor Agents
G-Protein-Coupled Receptors
GTP-Binding Proteins
Smooth Muscle Myocytes
Blood Vessels
Endothelial Cells
Binding Sites
Pharmacology
Kidney
Lung
Messenger RNA

ASJC Scopus subject areas

  • General

Cite this

Sakurai, T., Yanagisawa, M., Takuwa, Y., Miyazaki, H., Kimura, S., Goto, K., & Masaki, T. (1990). Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. Nature, 348(6303), 732-735.

Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. / Sakurai, Takeshi; Yanagisawa, Masashi; Takuwa, Yoh; Miyazaki, Hitoshi; Kimura, Sadao; Goto, Katsutoshi; Masaki, Tomoh.

In: Nature, Vol. 348, No. 6303, 20.12.1990, p. 732-735.

Research output: Contribution to journalArticle

Sakurai, T, Yanagisawa, M, Takuwa, Y, Miyazaki, H, Kimura, S, Goto, K & Masaki, T 1990, 'Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor', Nature, vol. 348, no. 6303, pp. 732-735.
Sakurai T, Yanagisawa M, Takuwa Y, Miyazaki H, Kimura S, Goto K et al. Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. Nature. 1990 Dec 20;348(6303):732-735.
Sakurai, Takeshi ; Yanagisawa, Masashi ; Takuwa, Yoh ; Miyazaki, Hitoshi ; Kimura, Sadao ; Goto, Katsutoshi ; Masaki, Tomoh. / Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. In: Nature. 1990 ; Vol. 348, No. 6303. pp. 732-735.
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