The human endothelin family

Three structurally and pharmacologically distinct isopeptides predicted by three separate genes

A. Inoue, Masashi Yanagisawa, S. Kimura, Y. Kasuya, T. Miyauchi, K. Goto, T. Masaki

Research output: Contribution to journalArticle

2453 Citations (Scopus)

Abstract

Three distinct human endothelin-related genes were cloned by screening a genomic DNA library under a low hyrbidization stringency with a synthetic oligonucleotide probe encoding a portion of the endothelin sequence. Genomic Southern blot analysis with the same oligonucleotide probe showed three corresponding chromosomal loci not only in the human genome but also in porcine and rat genomes. The nucleotide sequences of the three human genes were highly conserved within the regions encoding 21-residue (mature) endothelins, in spite of the fact that the immediately upstream exon sequences, which encode a part of the propeptides, retained little similarity. Moreover, each of the human genes predicted a putative 21-residue peptide, similar to but distinct from each other: (i) the 'classical' endothelin (ET-1), (ii) [Trp6,Leu7]endothelin (ET-2), and (iii) [Thr2,Phe4,Thr5,Tyr6,Lys7,Tyr14]endothelin (ET-3). Synethetic ET-1, ET-2, and ET-3 were prepared according to the deduced amino acid sequences, and the biological activities were assayed by contraction of isolated porcine coronary artery strips and by intravenous injection to anesthetized rats. All these synthetic peptides produced strong vasoconstrictor and pressor responses. However, the quantitative profiles of the pharmacological activities were considerably different among the three isopeptides, suggesting the possible existence of endothelin receptor subtypes.

Original languageEnglish (US)
Pages (from-to)2863-2867
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number8
StatePublished - 1989

Fingerprint

Endothelins
Oligonucleotide Probes
Swine
Endothelin-2
Endothelin-3
Genes
Endothelin Receptors
Peptides
Genomic Library
Vasoconstrictor Agents
Endothelin-1
Human Genome
Southern Blotting
Gene Library
Intravenous Injections
Amino Acid Sequence
Exons
Coronary Vessels
Genome
Pharmacology

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

The human endothelin family : Three structurally and pharmacologically distinct isopeptides predicted by three separate genes. / Inoue, A.; Yanagisawa, Masashi; Kimura, S.; Kasuya, Y.; Miyauchi, T.; Goto, K.; Masaki, T.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 86, No. 8, 1989, p. 2863-2867.

Research output: Contribution to journalArticle

@article{a44d3cb6240646948a3b7d3ac583744b,
title = "The human endothelin family: Three structurally and pharmacologically distinct isopeptides predicted by three separate genes",
abstract = "Three distinct human endothelin-related genes were cloned by screening a genomic DNA library under a low hyrbidization stringency with a synthetic oligonucleotide probe encoding a portion of the endothelin sequence. Genomic Southern blot analysis with the same oligonucleotide probe showed three corresponding chromosomal loci not only in the human genome but also in porcine and rat genomes. The nucleotide sequences of the three human genes were highly conserved within the regions encoding 21-residue (mature) endothelins, in spite of the fact that the immediately upstream exon sequences, which encode a part of the propeptides, retained little similarity. Moreover, each of the human genes predicted a putative 21-residue peptide, similar to but distinct from each other: (i) the 'classical' endothelin (ET-1), (ii) [Trp6,Leu7]endothelin (ET-2), and (iii) [Thr2,Phe4,Thr5,Tyr6,Lys7,Tyr14]endothelin (ET-3). Synethetic ET-1, ET-2, and ET-3 were prepared according to the deduced amino acid sequences, and the biological activities were assayed by contraction of isolated porcine coronary artery strips and by intravenous injection to anesthetized rats. All these synthetic peptides produced strong vasoconstrictor and pressor responses. However, the quantitative profiles of the pharmacological activities were considerably different among the three isopeptides, suggesting the possible existence of endothelin receptor subtypes.",
author = "A. Inoue and Masashi Yanagisawa and S. Kimura and Y. Kasuya and T. Miyauchi and K. Goto and T. Masaki",
year = "1989",
language = "English (US)",
volume = "86",
pages = "2863--2867",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "8",

}

TY - JOUR

T1 - The human endothelin family

T2 - Three structurally and pharmacologically distinct isopeptides predicted by three separate genes

AU - Inoue, A.

AU - Yanagisawa, Masashi

AU - Kimura, S.

AU - Kasuya, Y.

AU - Miyauchi, T.

AU - Goto, K.

AU - Masaki, T.

PY - 1989

Y1 - 1989

N2 - Three distinct human endothelin-related genes were cloned by screening a genomic DNA library under a low hyrbidization stringency with a synthetic oligonucleotide probe encoding a portion of the endothelin sequence. Genomic Southern blot analysis with the same oligonucleotide probe showed three corresponding chromosomal loci not only in the human genome but also in porcine and rat genomes. The nucleotide sequences of the three human genes were highly conserved within the regions encoding 21-residue (mature) endothelins, in spite of the fact that the immediately upstream exon sequences, which encode a part of the propeptides, retained little similarity. Moreover, each of the human genes predicted a putative 21-residue peptide, similar to but distinct from each other: (i) the 'classical' endothelin (ET-1), (ii) [Trp6,Leu7]endothelin (ET-2), and (iii) [Thr2,Phe4,Thr5,Tyr6,Lys7,Tyr14]endothelin (ET-3). Synethetic ET-1, ET-2, and ET-3 were prepared according to the deduced amino acid sequences, and the biological activities were assayed by contraction of isolated porcine coronary artery strips and by intravenous injection to anesthetized rats. All these synthetic peptides produced strong vasoconstrictor and pressor responses. However, the quantitative profiles of the pharmacological activities were considerably different among the three isopeptides, suggesting the possible existence of endothelin receptor subtypes.

AB - Three distinct human endothelin-related genes were cloned by screening a genomic DNA library under a low hyrbidization stringency with a synthetic oligonucleotide probe encoding a portion of the endothelin sequence. Genomic Southern blot analysis with the same oligonucleotide probe showed three corresponding chromosomal loci not only in the human genome but also in porcine and rat genomes. The nucleotide sequences of the three human genes were highly conserved within the regions encoding 21-residue (mature) endothelins, in spite of the fact that the immediately upstream exon sequences, which encode a part of the propeptides, retained little similarity. Moreover, each of the human genes predicted a putative 21-residue peptide, similar to but distinct from each other: (i) the 'classical' endothelin (ET-1), (ii) [Trp6,Leu7]endothelin (ET-2), and (iii) [Thr2,Phe4,Thr5,Tyr6,Lys7,Tyr14]endothelin (ET-3). Synethetic ET-1, ET-2, and ET-3 were prepared according to the deduced amino acid sequences, and the biological activities were assayed by contraction of isolated porcine coronary artery strips and by intravenous injection to anesthetized rats. All these synthetic peptides produced strong vasoconstrictor and pressor responses. However, the quantitative profiles of the pharmacological activities were considerably different among the three isopeptides, suggesting the possible existence of endothelin receptor subtypes.

UR - http://www.scopus.com/inward/record.url?scp=0013543367&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0013543367&partnerID=8YFLogxK

M3 - Article

VL - 86

SP - 2863

EP - 2867

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 8

ER -