A specific, photolabile and irreversible antagonist (L662,025) of the PAF-receptor.
PAF (0.2 microM) induced maximal platelet aggregation in human PRP and [3H]-PAF (1-5 nM) binding to platelet membrane preparations had Kd value of 3.8 nM and Bmax of 200 fmoles/mg of protein. Without UV irradiation, a synthetic azido tetrahydrofuran derivative L662,025 was a reversible and competitive PAF-receptor antagonist with IC50 values of 5.6 +/- 0.3 microM (platelet aggregation) and 1.0 +/- 0.25 microM (receptor binding). Photolysis of L662,025 in the presence of PRP produced an irreversible inhibition of platelet aggregation and specific binding of [3H]-PAF (1 nM). L662,025 did not affect collagen- or ADP-induced human platelet aggregation before or after photolysis. It is a new probe that can be used to identify and characterize the PAF-receptor.
Hussaini
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Department of Chemistry, University of Virginia, Charlottesville 22901.
Shen
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D001386:Azides / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000187:drug effects*; D043562:Receptors, G-Protein-Coupled; D013056:Spectrophotometry, Ultraviolet
D001386:Azides; D005663:Furans; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C059982:L 662025