Effect of YM471, a nonpeptide AVP receptor antagonist, on human coronary artery smooth muscle cells.

Abstract

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.

• Authors: Atsuo Tahara, Junko Tsukada, Yuichi Tomura, Koh-ichi Wada, Toshiyuki Kusayama, Noe Ishii, Takeyuki Yatsu, Wataru Uchida, Nobuaki Taniguchi, Akihiro Tanaka
• Journal: Peptides (Peptides) Vol. 23 Issue 10 Pg. 1809-16 (Oct 2002) ISSN: 0196-9781 [Print] United States
• PMID: 12383869 (Publication Type: Comparative Study, Journal Article)

Chemical References

• 4'-(4,4-difluoro-5-(2-(4-dimethylaminopiperidino)-2-oxoethylidene)-2,3,4,5-tetrahydro-1H-1-benzoazepine-1-carbonyl)-2-phenylbenzanilide
• Antidiuretic Hormone Receptor Antagonists
• Azepines
• Culture Media, Serum-Free
• Ligands
• Piperidines
• Oxytocin
• Calcium

Topics

• Antidiuretic Hormone Receptor Antagonists
• Arteries (cytology)
• Azepines (pharmacology)
• Binding, Competitive (drug effects)
• Calcium (metabolism)
• Cell Division (drug effects)
• Cell Membrane (drug effects, metabolism)
• Cells, Cultured
• Coronary Vessels (anatomy & histology)
• Culture Media, Serum-Free
• Dose-Response Relationship, Drug
• Humans
• Inhibitory Concentration 50
• Ligands
• Muscle, Smooth, Vascular (drug effects, metabolism)
• Oxytocin (metabolism)
• Piperidines (pharmacology)