Effects of nonsteroid antiinflammatory drugs on the specific binding of platelet activating factor to membrane preparations of rabbit platelets.

Abstract:

:The inhibitory effects of several antiinflammatory agents on the specific binding of tritiated 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphorylcholine, (platelet activating factor, PAF), with its receptor on isolated rabbit platelet plasma membranes were investigated. Several potent cyclooxygenase inhibitors do not inhibit 3H-PAF binding to its receptor sites. Yet, three others, indomethacin, phenylbutazone and sulfinpyrazone, as well as three non-cyclooxygenase inhibitors, the 3',4'-dimethoxy analog of indomethacin, the prodrug sulindac and its sulfone metabolite, are moderately active at relatively high concentrations (50 - 100 microM). Parallel inhibitions of 3H-PAF binding and PAF-induced platelet aggregation by derivatives of these antiinflammatory agents suggest that these inhibitors are probably interacting with the functional binding sites of PAF. The results clearly indicate that the configuration of PAF binding site is very different from the inhibitory site of cyclooxygenase. A preference for oxygenated substituents in these hydrophobic molecules to inhibit the PAF-receptor binding is noted. Some binding characteristics of the receptor are briefly discussed.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Hwang SB,Cheah MJ,Lee CS,Shen TY

doi

10.1016/0049-3848(84)90256-1

subject

Has Abstract

pub_date

1984-06-15 00:00:00

pages

519-31

issue

6

eissn

0049-3848

issn

1879-2472

pii

0049-3848(84)90256-1

journal_volume

34

pub_type

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