Inhibition by CV-3988 of the binding of [3H]-platelet activating factor (PAF) to the platelet.
The inhibitory effects of CV-3988, a specific antagonist of PAF, on the binding of [3H]-PAF to washed platelets of various species including human were examined. The dissociation constant (Kd), binding capacity (Bmax), and the number of receptor/platelet for the specific binding site of rabbit platelets were 2.2 +/- 0.2 nM, 93.7 +/- 8.3 fmoles/10(8) platelets, and 568 +/- 50, respectively. CV-3988 selectively inhibited the specific binding of [3H]-PAF to rabbit platelets with an IC50 of 7.9 X 10(-8) M, and it slightly increased the Kd value (2.5 +/- 0.8 nM) and decreased the binding capacity for PAF (Bmax: 54.3 +/- 16.3 fmoles/10(8) platelets). The Ki value of CV-3988 for the specific binding of [3H]-PAF to rabbit platelets was 1.2 X 10(-7) M. CV-3988 had no effects on the binding of [3H]-5-hydroxytryptamine (5-HT) to rabbit platelets and on the shape change of the platelet induced by 5-HT. CV-3988 also inhibited the specific binding of [3H]-PAF to human and guinea-pig platelets with IC50 values of 1.6 X 10(-7) and 1.8 X 10(-7) M, respectively. CV-3988 inhibited the PAF-induced aggregation in rabbit, guinea-pig, and human platelets. These findings show that CV-3988 is a specific antagonist of PAF at the receptor site(s) of platelets and, in these species, inhibits PAF-induced platelet aggregation by inhibiting the binding of PAF to the "PAF receptor". No specific binding of [3H]-PAF to the platelet of rats and mice was observed, indicating that these species lack a PAF receptor.
Terashita
Z
Z
Imura
Y
Y
Nishikawa
K
K
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D003864:Depression, Chemical; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins; D011817:Rabbits; D051381:Rats; D011956:Receptors, Cell Surface / Q000032:analysis; D043562:Receptors, G-Protein-Coupled; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D013045:Species Specificity; D013844:Thiazoles / Q000494:pharmacology*; D014316:Tritium
D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013844:Thiazoles; C039351:platelet activating factor receptor; D014316:Tritium; D012701:Serotonin; C037913:CV 3988