The single prostacyclin receptor of gel-filtered platelets provides a correlation with antiaggregatory potency of PGI2 mimics

Thomas L. Eggerman; Cynthia J. Hartzell; Sara Selfe; Niels H. Andersen

doi:10.1016/0049-3848(87)90327-6

The single prostacyclin receptor of gel-filtered platelets provides a correlation with antiaggregatory potency of PGI₂ mimics

Thomas L. Eggerman, Cynthia J. Hartzell, Sara Selfe, Niels H. Andersen

Chemistry and Biochemistry

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Gel-filtered human platelets (GFP) display only a single binding site for [³H]-PGI₂: K_D=61nM, 234 fmol/10⁸ platelets (1410 sites/platelet). Platelet-rich plasma (PRP) displays the same receptor density but the K_D 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.

Original language	English (US)
Pages (from-to)	645-659
Number of pages	15
Journal	Thrombosis Research
Volume	45
Issue number	5
DOIs	https://doi.org/10.1016/0049-3848(87)90327-6
State	Published - Mar 1 1987

Keywords

aggregation inhibition
platelets
prostacyclin
receptor
structure-activity-relationships

ASJC Scopus subject areas

Hematology

Access to Document

10.1016/0049-3848(87)90327-6

Cite this

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title = "The single prostacyclin receptor of gel-filtered platelets provides a correlation with antiaggregatory potency of PGI2 mimics",

abstract = "Gel-filtered human platelets (GFP) display only a single binding site for [3H]-PGI2: KD=61nM, 234 fmol/108 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.",

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author = "Eggerman, {Thomas L.} and Hartzell, {Cynthia J.} and Sara Selfe and Andersen, {Niels H.}",

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N2 - Gel-filtered human platelets (GFP) display only a single binding site for [3H]-PGI2: KD=61nM, 234 fmol/108 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.

AB - Gel-filtered human platelets (GFP) display only a single binding site for [3H]-PGI2: KD=61nM, 234 fmol/108 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.

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