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Putative precursors of endothelin have less vasoconstrictor activity in vitro but a potent pressor effect in vivo
Author(s) -
Kashiwabara Tomoko,
Inagaki Yoshimasa,
Ohta Hideo,
Iwamatsu Akihiro,
Nomizu Motoyoshi,
Morita Akihito,
Nishikori Koji
Publication year - 1989
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(89)81243-8
Subject(s) - in vivo , endothelin receptor , contraction (grammar) , chemistry , in vitro , endocrinology , vasoconstrictor agents , blood pressure , medicine , endothelin 1 , bolus (digestion) , endothelins , pharmacology , biology , biochemistry , receptor , microbiology and biotechnology
Endothelin (ET‐21) induced a sustained contraction of rat thoracic aortae (EC 50 =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 (EC 50 =3.26 × 10 −8 M), and so did the precursor from human cDNA (hET‐38) (EC 50 =1.48 × 10 −8 M). 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.