Binding characteristics of YM087, an AVP receptor antagonist, in rhesus monkey liver and kidney membranes.
The binding characteristics of YM087, a nonpeptide vasopressin (AVP) V1A and V2 receptor antagonist, were studied using 3H-AVP binding to rhesus monkey liver and kidney membrane preparations. Both membrane preparations exhibited one class of high-affinity binding sites. However each membrane's receptors were different, with Kd values of 0.57 and 1.11 nM, Bmax values of 59.6 and 147 fmol/mg protein for liver and kidney, respectively. AVP receptor agonist or antagonist binding inhibition studies confirmed that these receptors belong to the V1A (liver) and V2 (kidney) subtypes. YM087 showed high affinity for both liver V1A and kidney V2 receptors with Ki values of 26.3 and 9.89 nM, respectively. These results show that YM087 is a potent, nonpeptide dual AVP V1A and V2 receptor antagonist, and would be a powerful tool for understanding the physiologic roles of AVP.
Tahara
A
A
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., Ibaraki, Japan. tahara@yamanouchi.co.jp
Tomura
Y
Y
Wada
K
K
Kusayama
T
T
Tsukada
J
J
Ishii
N
N
Yatsu
T
T
Uchida
W
W
Tanaka
A
A
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000378:metabolism*; D001667:Binding, Competitive; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D008566:Membranes / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; C106389:conivaptan