BINDING CHARACTERISTICS OF YM087, AN AVP RECEPTOR ANTAGONIST, IN RHESUS-MONKEY LIVER AND KIDNEY MEMBRANES

The binding characteristics of YMO87, a nonpeptide vasopressin (AVP) V -1A and V-2 receptor antagonist, were studied using H-3-AVP binding to rhesus monkey liver and kidney membrane preparations. Both membrane p reparations exhibited one class of high-affinity binding sites. Howeve r each membrane's receptors were different, with K-d values of 0.57 an d 1.11 nM, B-max values of 59.6 and 147 fmol/mg protein for liver and kidney, respecrively. AVP receptor agonist or antagonist binding inhib ition 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, re spectively. These results show that YM087 is a potent, nonpeptide dual AVP V-1A and V-2 receptor antagonist, and would be a powerful tool fo r understanding the physiologic roles of AVP. (C) 1998 Elsevier Scienc e Inc.