Inhibition of the metabolism of platelet activating factor (PAF-acether) by three specific antagonists from Ginkgo biloba.
Washed rabbit platelet suspensions were incubated in the presence of 1-[3H]O-alkyl-2-acetyl-sn-glycero-3-phosphocholine ([3H] PAF-acether), which was metabolized into 1-[3H]O-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkylacyl-GPC) through the sequential action of cytosolic acetylhydrolase and membrane transacylase. Within 60 min at 37 degrees, percentage of [3H] PAF-acether metabolized was 50.3 +/- 5.2% (9 experiments). This conversion was inhibited in a dose-dependent manner by various concentrations of ginkgolides A, B and C (BN 52020, 52021, 52022) known as specific antagonists of PAF-acether. The three compounds displayed the following order of potency: BN 52021 (IC50 = 3.6 X 10(-6) M) greater than BN 52020 (IC50 = 9.7 X 10(-6) M) greater than BN 52022 (IC50 = 37.6 X 10(-6) M). As this order is the same as that previously defined for inhibition of platelet aggregation to PAF-acether or for inhibition of PAF-acether binding to platelets, our data bring further support to the view that PAF-acether metabolism in platelets involves in some way its binding to its membrane receptor.
Lamant
V
V
Mauco
G
G
Braquet
P
P
Chap
H
H
Douste-Blazy
L
L
D000818:Animals; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D046934:Ginkgolides; D007783:Lactones; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D008565:Membrane Proteins; D010936:Plant Extracts; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C045856:ginkgolide B