Biomaterial Database

Inhibition by CV-3988 of the binding of [3H]-platelet activating factor (PAF) to the platelet. 1985

Z Terashita, and Y Imura, and K Nishikawa

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010742	Phospholipid Ethers	Phospholipids which have an alcohol moiety in ethereal linkage with a saturated or unsaturated aliphatic alcohol. They are usually derivatives of phosphoglycerols or phosphatidates. The other two alcohol groups of the glycerol backbone are usually in ester linkage. These compounds are widely distributed in animal tissues.	Ether Phosphatidates,Ether Phospholipids,Glycerol Phosphate Ethers,Glycerophosphate Ethers,1-Alkyl-2-Acylphosphatidates,1 Alkyl 2 Acylphosphatidates,Ethers, Glycerol Phosphate,Ethers, Glycerophosphate,Ethers, Phospholipid,Phosphate Ethers, Glycerol,Phosphatidates, Ether,Phospholipids, Ether
D010972	Platelet Activating Factor	A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.	AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D010974	Platelet Aggregation	The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.	Aggregation, Platelet
D010980	Platelet Membrane Glycoproteins	Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.	PM-GP,Platelet Glycoprotein,Platelet Membrane Glycoprotein,PM-GPs,Platelet Glycoproteins,Glycoprotein, Platelet,Glycoprotein, Platelet Membrane,Glycoproteins, Platelet,Glycoproteins, Platelet Membrane,Membrane Glycoprotein, Platelet,Membrane Glycoproteins, Platelet,PM GP
D011817	Rabbits	A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes.	Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D011956	Receptors, Cell Surface	Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.	Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D001792	Blood Platelets	Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.	Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D003864	Depression, Chemical	The decrease in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.	Chemical Depression,Chemical Depressions,Depressions, Chemical
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea