Effect of YM471, a nonpeptide AVP receptor antagonist,on human coronary artery smooth muscle cells |
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Authors: | Tahara Atsuo Tsukada Junko Tomura Yuichi Wada Koh-ichi Kusayama Toshiyuki Ishii Noe Yatsu Takeyuki Uchida Wataru Taniguchi Nobuaki Tanaka Akihiro |
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Affiliation: | Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, 305-8585 Ibaraki, Japan. tahara@yamanouchi.co.jp |
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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. |
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