Adenosine receptor binding of the A1-selective antagonist (/sup 3/H)PD 116,948

Conference · Wed Mar 05 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:7024767

Fergus, J H; Bruns, R F; Badger, E W; Bristol, J A; Hartman, J D; Santay, L A; Hays, S J; Huang, C C

PD 116,948 (8-cyclopentyl-1,3-dipropylxanthine) is a potent adenosine (ado) antagonist which is highly selective for the A1 subtype of ado receptor, with an IC50 of 0.8 nM in (/sup 3/H)CHA binding to A1 receptors and 500 nM in (/sup 3/H)NECA binding to A2 receptors. (/sup 3/H)PD 116,948 (117 Ci/mmol) was prepared by reduction of the diallyl analog, and binding was performed at 25/sup 0/C in 2 ml of 50 mM Tris pH 7.7 for 60 min using membranes from 10 mg wet weight of rat whole brain, with 100 ..mu..M N/sup 6/-cyclopentylado used to define nonspecific binding. Under these conditions, (/sup 3/H)PD 116,948 bound to a single site with a K/sub d/ of 0.4 nM and a B/sub max/ of 46 pmol/g wet weight. Under optimal conditions, more than 99% of the binding of (/sup 3/H)PD 116,948 was specific. Affinities of ado agonists and antagonists versus 0.1 nM (/sup 3/H)PD 116,948 were highly consistent with binding to an A1 ado receptor. Substantial amounts of specific binding of (/sup 3/H)PD 116,948 were detected in testes and spleen, and smaller amounts were found in heart. (/sup 3/H)PD 116,948 should be a useful tool for labeling A1 receptors in the brain and other organs.

• Research Organization: Warner-Lambert/Parke-Davis Pharmaceutical Research, Ann Arbor, MI
• OSTI ID: 7024767
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:4
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADENOSINE
AFFINITY
ANIMALS
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
GONADS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MALE GENITALS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RIBOSIDES
RODENTS
SPLEEN
TESTES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES