Paper| Volume 37, ISSUE 4, P493-502, February 15, 1985

Differential inhibition of platelet thromboxane and lung prostacyclin production by sulphinpyrazone, acetylsalicylic acid and indomethacin by human tissues in vitro

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      To compare the inhibition of human platelet and lung cyclo-oxygenases by sulphinpyrazone (SP), acetylsali-cylic acid (ASA) and indomethacin, we investigated their effects on platelet thromboxane A2 (TxA2) production during spontaneous clotting and on prostacyclin (PGI2) and TxA2 productions of superfused minced human lung. The synthesis of proaggregatory, vasoconstricting TxA2 and antiaggregatory, vasodilating PGI2 were evaluated by measuring the concentration of their stable metabolites thromboxane B2 (TxB2) and 6-keto-prosta- glandin F respectively, by radioimmunoassays. The basal platelet TxB2 production was 241.0 + 56.3 ng/ml (mean ± SEM, n = 12). The concentrations needed for 50 % inhibition of this production (IC50) were 41.3 μmol/1 for sulphinpyrazone, 6.3 μmol/1 for ASA and 0.094 μmol/1 for indomethacin. The lung generated 23.8 ± 5.5 ng/g/min (mean + SEM, n = 6) of 6-keto-PGF and 8.5 ± 1.8 ng/g/ min of TxB2. The IC50 values for pulmonary 6-keto-PGF and TxB2 productions were 530.0 μmol/1 for SP, 370.0 μmol/1 for ASA and 50.0 μmol/1 for indomethacin. Thus pulmonary cyclo-oxygenase, presumably originating from endothelial cells, was 13, 59, and 532 times more resistant to these prostaglandin synthesis inhibitors (PGI's) than platelet cyclo-oxygenase. These data suggest that there are considerable differences in the concentration ranges of various PGI's by which the PGI2/TxA2 balance can be shifted to a dominance of PGI2.


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