The single prostacyclin receptor of gel-filtered platelets provides a correlation with antiaggregatory potency of PGI2 mimics.
Gel-filtered human platelets (GFP) display only a single binding site for [3H]-PGI2: KD = 61nM, 234 fmol/10(8) platelets (1410 sites/platelet). Platelet-rich plasma (PRP) displays the same receptor density but the KD value increases to 123 nM due to protein binding of PGI2 which lowers its effective concentration. The [3H]-PGI2/GFP binding assay has been used to evaluate the molecular basis of aggregation inhibition for prostacyclin analogs and mimics, three PGE type structures, and PGD2. Antiaggregatory IC50s and radioligand binding IC50s correlate for PGE2, E1, and six PGI2 analogs. PGD2, and to a lesser extent 6-oxo-PGE1, display greater antiaggregatory potency than expected based on PGI2-binding site affinity data.
Eggerman
T L
TL
Hartzell
C J
CJ
Selfe
S
S
Andersen
N H
NH
D001665:Binding Sites; D001792:Blood Platelets / Q000648:ultrastructure*; D002850:Chromatography, Gel; D003429:Cross Reactions; D011464:Epoprostenol / Q000378:metabolism; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000502:physiology*; D014316:Tritium
D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D014316:Tritium; D011464:Epoprostenol