-transparent.png){kind=logo}
The effects of FR139317 on the cardiovascular system were investigated in cultured cells, isolated organs and whole animals. FR139317 inhibited the specific binding of [125]endothelin(ET)-1 to porcine aortic microsomes in a concentration-dependent, monophasic fashion with an IC50 of 0.53 nM. In contrast, FR139317 showed low affinity for [125I]ET-1 specific binding sites in porcine kidney (IC50, 4.7 microM). In isolated rabbit aorta, FR139317 shifted the ET-1-induced concentration-contractile response curve to the right with a pA2 value of 7.2 and lacked agonist activity. A single (i.v.) bolus dose of FR139317 completely inhibited the pressor response to ET-1 in vivo, but had no effect on the initial depressor response in conscious normotensive rats. These data indicate that FR139317 is a potent, highly specific ETA receptor antagonist. In addition, FR139317 also inhibited ET-1 induced [3H]thymidine incorporation in cultured vascular smooth muscle cells from rat aorta (IC50, 4.1 nM), suggesting that ET-1-induced mitogenesis is mediated only by the ETA receptor. FR139317 could become a useful tool for investigating the physiological and pharmacological actions of ET.
K Sogabe, and
H Nirei, and
M Shoubo, and
A Nomoto, and
S Ao, and
Y Notsu, and
T Ono
September 1999,
The Journal of pharmacology and experimental therapeutics,
K Sogabe, and
H Nirei, and
M Shoubo, and
A Nomoto, and
S Ao, and
Y Notsu, and
T Ono
August 1996,
European journal of pharmacology,
K Sogabe, and
H Nirei, and
M Shoubo, and
A Nomoto, and
S Ao, and
Y Notsu, and
T Ono
October 1994,
Neuropharmacology,
K Sogabe, and
H Nirei, and
M Shoubo, and
A Nomoto, and
S Ao, and
Y Notsu, and
T Ono
January 1992,
Journal of cardiovascular pharmacology,
K Sogabe, and
H Nirei, and
M Shoubo, and
A Nomoto, and
S Ao, and
Y Notsu, and
T Ono
August 1992,
Blood pressure,
K Sogabe, and
H Nirei, and
M Shoubo, and
A Nomoto, and
S Ao, and
Y Notsu, and
T Ono
June 1999,
The Journal of pharmacology and experimental therapeutics,
K Sogabe, and
H Nirei, and
M Shoubo, and
A Nomoto, and
S Ao, and
Y Notsu, and
T Ono
August 1998,
The Journal of pharmacology and experimental therapeutics,
K Sogabe, and
H Nirei, and
M Shoubo, and
A Nomoto, and
S Ao, and
Y Notsu, and
T Ono
May 1994,
Proceedings of the National Academy of Sciences of the United States of America,
K Sogabe, and
H Nirei, and
M Shoubo, and
A Nomoto, and
S Ao, and
Y Notsu, and
T Ono
October 1994,
Chemical & pharmaceutical bulletin,
K Sogabe, and
H Nirei, and
M Shoubo, and
A Nomoto, and
S Ao, and
Y Notsu, and
T Ono
January 2017,
Nihon yakurigaku zasshi. Folia pharmacologica Japonica,
