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.
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U2 - 10.1073/pnas.86.8.2863
DO - 10.1073/pnas.86.8.2863
M3 - Article
C2 - 2649896
AN - SCOPUS:0013543367
SN - 0027-8424
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
IS - 8
ER -