CHARACTERIZATION OF THE BINDING OF [H-3] L-158,809 - A NEW POTENT AND SELECTIVE NONPEPTIDE ANGIOTENSIN-II RECEPTOR (AT(1)) ANTAGONIST RADIOLIGAND

[H-3]L-158,809, a new potent and AT1-selective nonpeptide angiotensin II receptor antagonist, bound saturably and reversibly to rat adrenal membranes. Scatchard and Hill plot analyses indicated a single class of high affinity (K(d) = 0.66 nm) binding sites. The relative potencies of various angiotensin II-related peptide and nonpeptide antagonists in displacing [H-3]L-1 58,809 binding correlated with their potencies in displacing the binding of I-125-Sar1,Ile8-angiotensin II to adrenal AT1 receptors. [H-3]L-158, 809 binding to adrenal membranes was not affected by addition of guanosine-5'-(beta, gamma-imido)triphosphate or various pharmacological agents known to interact with other common peptide and nonpeptide receptor systems. The Potencies of angiotensin II receptor agonists, but not antagonists, in inhibiting specific [H-3]L-1 58,809 binding were decreased in the presence of guanosine-5'-(beta,gamma-imido)triphosphate. Specific [H-3]L-158,809 binding was also observed in rat liver and kidney. Collectively, the data indicate that [H-3]L-158,809 represents a new, potent, nonpeptide, antagonist radioligand suitable for the study of angiotensin II AT1 receptors.