CHARACTERIZATION OF THE FINDING OF [I-125] L-735,286 - A NEW NONPEPTIDE ANGIOTENSIN-II AT(1) RECEPTOR RADIOLIGAND

[I-125]L-735,286, a new potent and AT(1)-selective nonpeptide angioten sin II receptor radioligand, bound saturably to whole adrenal membrane s. Scatchard and Hill plot analysis indicates a single class of high a ffinity (K-d = 0.5 nM) binding sites. The potencies of various angiote nsin II agonists and antagonists in displacing specific [I-125]L-735,2 86 binding are in good agreement with their potencies in displacing th e binding of [I-125]Sar(1),Ile(8)-AII to adrenal AT(1) receptors. The AT(2) selective ligand, PD121981 had no effect on specific [I-125]L-73 5,286 binding. In autoradiographic studies using rat kidney slices, sp ecific labeling of [I-125]L-735,286 was abolished by coincubation with saralasin. Collectively, the data indicated that [I-125]L-735,286 rep resents a new, potent nonpeptide antagonist radioligand suitable for t he study of angiotensin II AT(1) receptors.