PD 115,199: an antagonist ligand for adenosine A2 receptors

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

OSTI ID:7024874

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

PD 115,199, N-(2-(dimethylamino)ethyl)-N-methyl-4-((2,3,6,-7-tetrahydro)-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)benzenesulfonamide, is an adenosine (ado) antagonist with high affinity at both the A1 and A2 subtypes of ado receptor, with an IC50 of 24 nM in (/sup 3/H)CHA binding to A1 receptors and 23 nM in (/sup 3/H)NECA binding to A2 receptors. (/sup 3/H)PD 115,199 (126 Ci/mmol) was prepared by reduction of the diallyl analog. In rat striatal membranes, dose-inhibition curves for the A1-selective ado antagonist PD 116,948 vs 0.5 nM (/sup 3/H)PD 115,199 were markedly biphasic, with 21% of specific binding representing A1 sites with an IC50 for PD 116,948 of 0.52 nM, and the remaining 79% representing apparent A2 sites with an IC50 for PD 116,948 of 163 nM. Subsequent experiments were done in the presence of 20 nM PD 116,948 to eliminate A1 binding. Under these conditions, about 80% of binding was specific. (/sup 3/H)PD 115,199 bound with high affinity (K/sub d/ 10 nM) to a limited number of sites (Bmax 120 pmol/g wet weight). Affinities of compounds in (/sup 3/H)PD 115,199 binding closely paralleled their affinities in (/sup 3/H)NECA binding. Ado antagonists were generally several fold more active vs (/sup 3/H)PD 115,199 than vs (/sup 3/H)NECA, whereas the reverse was the case for agonists. Binding was much higher in striatum than in other brain areas. These results indicate that (/sup 3/H)PD 115,199 binds to a high-affinity A2 receptor.

• Research Organization: Warner-Lambert/Parke-davis Pharmaceutical Research, Ann Arbor, MI
• OSTI ID: 7024874
• 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
ANIMALS
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIGANDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RIBOSIDES
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES