Characterization of the binding of [3H]L-158,809: a new potent and selective nonpeptide angiotensin II receptor (AT1) antagonist radioligand.
[3H]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 (Kd = 0.66 nM) binding sites. The relative potencies of various angiotensin II-related peptide and nonpeptide antagonists in displacing [3H]L-158,809 binding correlated with their potencies in displacing the binding of 125I-Sar1,Ile8-angiotensin II to adrenal AT1 receptors. [3H]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 [3H]L-158,809 binding were decreased in the presence of guanosine-5'-(beta,gamma-imido)triphosphate. Specific [3H]L-158,809 binding was also observed in rat liver and kidney. Collectively, the data indicate that [3H]L-158,809 represents a new, potent, nonpeptide, antagonist radioligand suitable for the study of angiotensin II AT1 receptors.
Chen
T B
TB
New Lead Pharmacology, Merck Research Laboratories, West Point, Pennsylvania 19486.
Lotti
V J
VJ
Chang
R S
RS
D000311:Adrenal Glands / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D019808:Losartan; D015394:Molecular Structure; D011869:Radioligand Assay; D051381:Rats; D013777:Tetrazoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D006165:Guanylyl Imidodiphosphate; C070967:L 158809; D019808:Losartan