Putative precursors of endothelin have less vasoconstrictor activity in vitro but a potent pressor effect in vivo

FEBS Letters

Nomizu, Motoyoshi¹  Morita, Akihito¹  Ohta, Hideo¹  Iwamatsu, Akihiro¹  Kashiwabara, Tomoko¹  Inagaki, Yoshimasa¹  Nishikori, Koji¹ 

[1] Pharmaceutical Laboratory, Kirin Brewery Co. Ltd, Soujamachi 1-chome 2-2, Maebashi, Gunma 371, Japan

关键词: Endothelin;    Precursor;    Arterial pressure;    Vasoconstriction;    (Rat aorta);    ET-21;    endothelin;    hET-38;    precursor deduced from human cDNA coding ET-21;    pET-39;    precursor deduced from porcine cDNA coding ET-21;    ECE;    endothelin converting enzyme;    MBP;    mean blood pressure;    EDRF;    endothelium-derived relaxing factor;    EC50;    the half effective concentration of peptides for vasoconstrictor activity;   

DOI  :  10.1016/0014-5793(89)81243-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Endothelin (ET-21) induced a sustained contraction of rat thoracic aortae (EC₅₀=2.65 × 10⁻¹⁰ M) in vitro, and caused a potent pressor effect in vivo after intravenous administration to rats. In contrast, the precursor deduced from porcine cDNA coding ET-21 (pET-39) had 100-fold less contractile activity in vitro (EC₅₀=3.26 × 10⁻⁸M), and so did the precursor from human cDNA (hET-38) (EC₅₀=1.48 × 10⁻⁸M). However, both pET-39 and hET-38 caused almost the same dose-dependent pressor effects as ET-21 in vivo. After intravenous bolus injection at 1 nmol/kg, ET-21 caused an initial transient drop of the arterial pressure, and then induced a gradual pressor effect. On the other hand, hET-38 caused only a gradual rise of the arterial pressure. There may be different mechanism(s) for ET-21 and hET-38 which induce changes in the arterial pressure in vivo.

【 授权许可】

Unknown