Binding Characteristics of YM087, an AVP Receptor Antagonist, in Rhesus Monkey Liver and Kidney Membranes

Abstract

The binding characteristics of YM087, a nonpeptide vasopressin (AVP) V 1A and V 2 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 K d values of 0.57 and 1.11 nM, B max 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 V 1A (liver) and V 2 (kidney) subtypes. YM087 showed high affinity for both liver V 1A and kidney V 2 receptors with K i values of 26.3 and 9.89 nM, respectively. These results show that YM087 is a potent, nonpeptide dual AVP V 1A and V 2 receptor antagonist, and would be a powerful tool for understanding the physiologic roles of AVP.