Putative precursors of endothelin have less vasoconstrictor activity in vitro but a potent pressor effect in vivo.
Endothelin (ET-21) induced a sustained contraction of rat thoracic aortae (EC50 = 2.65 x 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 x 10(-8) M), and so did the precursor from human cDNA (hET-38) (EC50 = 1.48 x 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.
Kashiwabara
T
T
Pharmaceutical Laboratory, Kirin Brewery Co., Ltd, Gunma, Japan.
Inagaki
Y
Y
Ohta
H
H
Iwamatsu
A
A
Nomizu
M
M
Morita
A
A
Nishikori
K
K
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D004730:Endothelium, Vascular; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D011498:Protein Precursors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D010455:Peptides; D011498:Protein Precursors; D000804:Angiotensin II