Specific binding of (/sup 3/H) dihydrokadsurenone to rabbit platelet membranes and its inhibition by platelet activating factor (PAF) and PAF receptor antagonists

Conference · Thu May 01 00:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6992481

Hwang, S B; Lam, M H; Chang, M N

Kadsurenone inhibits specifically and competitively the specific binding of (/sup 3/H) PAF to rabbit platelet membranes with a K/sub B/ of 9 x 10/sup -8/M. 5-propyl analog of kadsurenone (dihydrokadsurenone) retains roughly the same potency as kadsurenone. To confirm that the inhibitory effect on the specific (/sup 3/H) PAF binding by kadsurenone, dihydrokadsurenone or other PAF receptor antagonists is due to the blockage of the receptor site, (/sup 3/H) dihydrokadsurenone was synthesized. A saturable specific (/sup 3/H) dihydrokadsurenone binding was found with an equilibrium dissociation constant (K/sub D/) of 16.48 (+/- 0.03) nM. The total number of detectable binding sites is 2.32 (+/- 0.09) pmol/mg protein, which is exactly identical to the B/sub max/ of the PAF receptor sites (2.30 +/- (0.40) pmol/mg protein) under identical assay conditions. Both C/sub 16/ and C/sub 18/-PAF fully displaced the specific (/sup 3/H) dihydrokadsurenone (5 nM) binding with an identical ED/sub 50/ of 10/sup -9/M. Dihydrokadsurenone and kadsurenone also displaced the specific binding with roughly the same potency (ED/sub 50/ = 3.6 x 10/sup -8/M). L-652,731 is more potent with an ED/sub 50/ of 2 x 10/sup -8/ M. Ono-6240 and CV-3988 also displaced the binding with ED/sub 50/ of 10/sup -7/ and 4 x 10/sup -7/ M respectively. These results strongly suggest that PAF and these PAF receptor antagonists interact with a common binding site in the PAF receptor.

• Research Organization: Merck Sharp and Dohme Research Labs., Rahway, NJ
• OSTI ID: 6992481
• Report Number(s): CONF-8606151-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD COAGULATION FACTORS
BLOOD PLATELETS
BODY FLUIDS
CELL CONSTITUENTS
CELL MEMBRANES
COAGULANTS
DRUGS
HEMATOLOGIC AGENTS
INHIBITION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MEMBRANES
ORGANIC COMPOUNDS
PROTEINS
RABBITS
REACTION KINETICS
RECEPTORS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES