Effect of YM471, a nonpeptide AVP receptor antagonist, on human coronary artery smooth muscle cells.
The antagonistic properties of YM471, a potent nonpeptide vasopressin (AVP) V(1A) and V(2) receptor antagonist, were characterized using human coronary artery smooth muscle cells (CASMC). YM471 potently inhibited specific binding of 3H-AVP to V(1A) receptors on human CASMC, exhibiting a K(i) value of 0.49 nM. Furthermore, YM471 inhibited the AVP-induced increase in intracellular free Ca(2+) concentration with an IC(50) value of 1.42 nM, but exerted no agonistic activity on CASMC. Additionally, while AVP concentration-dependently induced hyperplasia and hypertrophy in CASMC, YM471 prevented these AVP-induced growth effects, exhibiting IC(50) values of 0.93 and 2.64 nM, respectively. These results indicate that YM471 has high affinity for V(1A) receptors on, and high potency in inhibiting AVP-induced physiologic responses of, human CASMC.
Tahara
Atsuo
A
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, 305-8585 Ibaraki, Japan. tahara@yamanouchi.co.jp
Tsukada
Junko
J
Tomura
Yuichi
Y
Wada
Koh-ichi
K
Kusayama
Toshiyuki
T
Ishii
Noe
N
Yatsu
Takeyuki
T
Uchida
Wataru
W
Taniguchi
Nobuaki
N
Tanaka
Akihiro
A
D065092:Antidiuretic Hormone Receptor Antagonists; D001158:Arteries / Q000166:cytology*; D001381:Azepines / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000033:anatomy & histology; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010121:Oxytocin / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*
C432083:4'-(4,4-difluoro-5-(2-(4-dimethylaminopiperidino)-2-oxoethylidene)-2,3,4,5-tetrahydro-1H-1-benzoazepine-1-carbonyl)-2-phenylbenzanilide; D065092:Antidiuretic Hormone Receptor Antagonists; D001381:Azepines; D016895:Culture Media, Serum-Free; D008024:Ligands; D010880:Piperidines; D010121:Oxytocin; D002118:Calcium