The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes.
-
- A Inoue
- Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
-
- M Yanagisawa
- Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
-
- S Kimura
- Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
-
- Y Kasuya
- Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
-
- T Miyauchi
- Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
-
- K Goto
- Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
-
- T Masaki
- Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
書誌事項
- 公開日
- 1989-04
- DOI
-
- 10.1073/pnas.86.8.2863
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:p>Three distinct human endothelin-related genes were cloned by screening a genomic DNA library under a low hybridization 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 the 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). Synthetic 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.</jats:p>
収録刊行物
-
- Proceedings of the National Academy of Sciences
-
Proceedings of the National Academy of Sciences 86 (8), 2863-2867, 1989-04
Proceedings of the National Academy of Sciences
