C. Serradeillegal et al., BINDING OF [H-3] SR-49059, A POTENT NONPEPTIDE VASOPRESSIN V-1A ANTAGONIST, TO RAT AND HUMAN LIVER MEMBRANES, Biochemical and biophysical research communications, 199(1), 1994, pp. 353-360
The new potent and selective nonpeptide vasopressin V-1a antagonist, S
R 49059, was tritiated and used for the characterization of rat and hu
man liver AVP V-1a receptors. Binding of [H-3] SR 49059 was time-depen
dent, reversible and saturable. A single class of high affinity bindin
g sites was identified with K-d values of 0.63 +/- 0.13 and 2.95 +/- 0
.64 nM, in rat and human liver membranes, respectively. The maximal bi
nding capacity (B-MAX) was about 7 times higher in rat than in human l
iver preparations. The relative potencies of several AVP/oxytocin agon
ists or antagonists to inhibit [H-3] SR 49059 binding confirmed that t
his ligand labeled a homogenous population of sites with the expected
AVP V-1a profile. Furthermore, [H-3] SR 49059 or unlabeled SR 49059 di
splayed only slight species differences between rat and human V-1a rec
eptors, whereas OPC-21268, another nonpeptide V-1a antagonist, exhibit
ed a high species-related potency with more than 500 fold higher affin
ity for rat than for human liver V-1a receptors. Thus, [H-3] SR 49059
is the first nonpeptide AVP V-1a ligand reported having highly specifi
c activity, stability, specificity and affinity. This makes it a suita
ble probe for labeling AVP V-1a receptors in rat and also in human tis
sues. (C) 1994 Academic Press, Inc.