title: [3H]A-81988, a potent, selective, competitive antagonist radioligand for angiotensin AT1 receptors.
abstract: Abbott-81988 (A-81988), 2-(N-n-Propyl-N-[(2'-[1H-tetrazol-5-yl]biphenyl-4- yl)methyl]amino)pyridine-3-carboxylic acid is a potent, competitive, non-peptidic antagonist of angiotensin AT1 receptors. A-81988 was labeled with tritium to high specific activity (16 Ci/mmol) and radioligand binding assays performed in rat liver membranes. [3H]A-81988 bound with high affinity (KD = 0.57 nM) and the KD determined from kinetics assays was similar. Non-specific binding (defined with 10(-6) M angiotensin-II) was very low (< 6% at the KD). The binding of [3H]A-81988 was competitive and exhibited appropriate pharmacological specificity for compounds acting at angiotensin AT1 receptors. These properties demonstrate that [3H]A-81988 will be a useful radioligand for studies of angiotensin AT1 receptors in various tissues.
authors.affiliation: Department 47C, AP-10, Abbott Laboratories, Abbott Park, IL 60064.
authors.forename: A A
authors.initials: AA
authors.lastname: Hancock
authors.forename: B W
authors.initials: BW
authors.lastname: Surber
authors.forename: G
authors.initials: G
authors.lastname: Rotert
authors.forename: S
authors.initials: S
authors.lastname: Thomas
authors.forename: A S
authors.initials: AS
authors.lastname: Tasker
authors.forename: B K
authors.initials: BK
authors.lastname: Sorensen
authors.forename: A D
authors.initials: AD
authors.lastname: Vodenlich
authors.forename: T J
authors.initials: TJ
authors.lastname: Opgenorth
authors.forename: D J
authors.initials: DJ
authors.lastname: Kerkman
authors.forename: J F
authors.initials: JF
authors.lastname: DeBernardis
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009539:Nicotinic Acids / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D009539:Nicotinic Acids; D013777:Tetrazoles; D000804:Angiotensin II; C081174:A 81988