Characterization of the binding of [125I]L-735,286: a new nonpeptide angiotensin II AT1 receptor radioligand.
[125I]L-735,286, a new potent and AT1-selective nonpeptide angiotensin II receptor radioligand, bound saturably to whole adrenal membranes. Scatchard and Hill plot analysis indicates a single class of high affinity (Kd = 0.5 nM) binding sites. The potencies of various angiotensin II agonists and antagonists in displacing specific [125I]L-735,286 binding are in good agreement with their potencies in displacing the binding of [125I]Sar1,Ile8-AII to adrenal AT1 receptors. The AT2 selective ligand, PD121981 had no effect on specific [125I]L-735,286 binding. In autoradiographic studies using rat kidney slices, specific labeling of [125I]L-735,286 was abolished by coincubation with saralasin. Collectively, the data indicated that [125I]L-735,286 represents a new, potent nonpeptide antagonist radioligand suitable for the study of angiotensin II AT1 receptors.
Chen
T B
TB
Department of New Lead Pharmacology, Merck Research Laboratories, West Point, Pennsylvania 19486.
Brenner
N J
NJ
Gibson
R E
RE
Burns
H D
HD
Chang
R S
RS
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001345:Autoradiography; D007668:Kidney / Q000737:chemistry; D008024:Ligands; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000032:analysis / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; C092285:L 735286; D008024:Ligands; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D009536:Niacinamide