Conversion of big endothelin-1 to 21-residue endothelin-1 is essential for expression of full vasoconstrictor activity: Structure-activity relationships of big endothelin-1

S. Kimura, Y. Kasuya, T. Sawamura, O. Shinmi, Y. Sugita, Masashi Yanagisawa, K. Goto, T. Masaki

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

The vasoconstrictor activities of porcine big endothelin-1 (big ET-1), a 39-residue intermediate predicted from cDNA sequence analysis, and of its shorter derivative, bit ET-1 [1-25], were characterized in vitro by measuring the contraction of porcine coronary artery strips. Synthetic big ET-1 [1-39] and big ET-1 [1-25] induced a slow developing, long-lasting, and strong vasoconstriction as in the case of 21-residue ET-1. However, the contractile molar potencies of big ET-1 [1-39] and big ET-1 [1-25] were approximately 140- and 50-fold lower than that of ET-1, respectively. These results indicate that the conversion of big ET-1 to 'mature' ET-1 is essential for the expression of the full vasoconstrictor activity, suggesting the physiological importance of the unusual proteolytic processing catalyzed by the putative 'ET converting enzyme'.

Original languageEnglish (US)
JournalJournal of Cardiovascular Pharmacology
Volume13
Issue numberSUPPL. 5
StatePublished - 1989

Fingerprint

Vasoconstrictor Agents
Endothelin-1
Structure-Activity Relationship
Swine
Vasoconstriction
Sequence Analysis
Coronary Vessels
Complementary DNA
Enzymes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Conversion of big endothelin-1 to 21-residue endothelin-1 is essential for expression of full vasoconstrictor activity : Structure-activity relationships of big endothelin-1. / Kimura, S.; Kasuya, Y.; Sawamura, T.; Shinmi, O.; Sugita, Y.; Yanagisawa, Masashi; Goto, K.; Masaki, T.

In: Journal of Cardiovascular Pharmacology, Vol. 13, No. SUPPL. 5, 1989.

Research output: Contribution to journalArticle

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abstract = "The vasoconstrictor activities of porcine big endothelin-1 (big ET-1), a 39-residue intermediate predicted from cDNA sequence analysis, and of its shorter derivative, bit ET-1 [1-25], were characterized in vitro by measuring the contraction of porcine coronary artery strips. Synthetic big ET-1 [1-39] and big ET-1 [1-25] induced a slow developing, long-lasting, and strong vasoconstriction as in the case of 21-residue ET-1. However, the contractile molar potencies of big ET-1 [1-39] and big ET-1 [1-25] were approximately 140- and 50-fold lower than that of ET-1, respectively. These results indicate that the conversion of big ET-1 to 'mature' ET-1 is essential for the expression of the full vasoconstrictor activity, suggesting the physiological importance of the unusual proteolytic processing catalyzed by the putative 'ET converting enzyme'.",
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AU - Kimura, S.

AU - Kasuya, Y.

AU - Sawamura, T.

AU - Shinmi, O.

AU - Sugita, Y.

AU - Yanagisawa, Masashi

AU - Goto, K.

AU - Masaki, T.

PY - 1989

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N2 - The vasoconstrictor activities of porcine big endothelin-1 (big ET-1), a 39-residue intermediate predicted from cDNA sequence analysis, and of its shorter derivative, bit ET-1 [1-25], were characterized in vitro by measuring the contraction of porcine coronary artery strips. Synthetic big ET-1 [1-39] and big ET-1 [1-25] induced a slow developing, long-lasting, and strong vasoconstriction as in the case of 21-residue ET-1. However, the contractile molar potencies of big ET-1 [1-39] and big ET-1 [1-25] were approximately 140- and 50-fold lower than that of ET-1, respectively. These results indicate that the conversion of big ET-1 to 'mature' ET-1 is essential for the expression of the full vasoconstrictor activity, suggesting the physiological importance of the unusual proteolytic processing catalyzed by the putative 'ET converting enzyme'.

AB - The vasoconstrictor activities of porcine big endothelin-1 (big ET-1), a 39-residue intermediate predicted from cDNA sequence analysis, and of its shorter derivative, bit ET-1 [1-25], were characterized in vitro by measuring the contraction of porcine coronary artery strips. Synthetic big ET-1 [1-39] and big ET-1 [1-25] induced a slow developing, long-lasting, and strong vasoconstriction as in the case of 21-residue ET-1. However, the contractile molar potencies of big ET-1 [1-39] and big ET-1 [1-25] were approximately 140- and 50-fold lower than that of ET-1, respectively. These results indicate that the conversion of big ET-1 to 'mature' ET-1 is essential for the expression of the full vasoconstrictor activity, suggesting the physiological importance of the unusual proteolytic processing catalyzed by the putative 'ET converting enzyme'.

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