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Inhibition by cardiolipins of platelet-activating factor-induced rabbit platelet activation
D Tsoukatos1, C A Demopoulos, A D Tselepis
1Department of Chemistry, School of Science, University of Ioannina, Greece.
Insights
Cardiolipin, a phospholipid, inhibits platelet aggregation induced by platelet-activating factor (paf). This suggests cardiolipin interacts with specific paf receptors on rabbit platelets.
Area of Science:
- Biochemistry
- Pharmacology
- Cell Biology
Background:
- Platelet aggregation plays a crucial role in hemostasis and thrombosis.
- Platelet-activating factor (paf) is a potent lipid mediator involved in various physiological and pathological processes, including platelet activation.
- Understanding the modulators of paf-induced platelet aggregation is essential for developing therapeutic strategies.
Purpose of the Study:
- To investigate the effect of cardiolipin and its derivatives on platelet aggregation induced by paf.
- To elucidate the mechanism by which cardiolipin influences paf-mediated platelet responses.
- To determine if cardiolipin's activity is specific to paf or affects other platelet agonists.
Main Methods:
- In vitro studies using washed rabbit platelets and platelet-rich plasma.
- Measurement of platelet aggregation induced by paf, adenosine diphosphate, and arachidonic acid.
- Determination of IC50 values for cardiolipin and phosphonocardiolipin inhibition of paf-induced aggregation.
- Investigation of the aggregatory effect of acetylated cardiolipin and its inhibition by paf antagonists.
- Assessment of platelet response to acetyl-cardiolipin after paf treatment.
Main Results:
- Cardiolipin and phosphonocardiolipin significantly inhibited paf-induced platelet aggregation in a dose-dependent manner.
- The IC50 values for cardiolipin were 8.4 x 10(-7) M and 2.6 x 10(-6) M for different paf concentrations.
- Phosphonocardiolipin showed an IC50 of 3 x 10(-7) M against paf-induced aggregation.
- Neither cardiolipin nor phosphonocardiolipin aggregated platelets or inhibited aggregation induced by adenosine diphosphate or arachidonic acid.
- Acetylated cardiolipin induced aggregation in aspirin-treated platelets, which was blocked by paf antagonists and rendered platelets insensitive to paf.
Conclusions:
- Cardiolipin acts as an inhibitor of paf-induced platelet aggregation.
- The inhibitory effect of cardiolipin appears to be mediated through specific paf receptors on the platelet membrane.
- Cardiolipin's action is specific to paf and does not affect aggregation induced by other agonists like ADP or arachidonic acid.
Abstract:
Evidence is presented that cardiolipin, a naturally occurring phospholipid, inhibits the aggregatory effect of platelet-activating factor (paf) on rabbit platelets in vitro. Bovine heart cardiolipin was shown to inhibit the aggregation of washed rabbit platelets induced by 1 x 10(-10) M and 2 x 10(-10) M paf with IC50 values (doses for half-maximal inhibition) of 8.4 +/- 0.8 x 10(-7) M and 2.6 +/- 0.6 x 10(-6) M, respectively. Phosphonocardiolipin was also able to inhibit platelet aggregation induced by 1 x 10(-10) M paf with an IC50 value of 3 +/- 1 x 10(-7) M. Both compounds, in concentrations up to 1 x 10(-5) M, were unable to aggregate washed rabbit platelets and failed to inhibit the aggregation induced by 0.9 and 1.8 microM adenosine diphosphate or 0.2-1.0 microM arachidonic acid. By contrast, the acetylated derivative of cardiolipin exerted an aggregatory effect on aspirin-treated rabbit platelets in the presence of creatine phosphate/creatine phosphokinase. This aggregation was inhibited by the specific paf antagonists BN 52021 and WEB 2086. Also, platelets treated with acetyl-cardiolipin were insensitive to the aggregatory effect of paf. Phosphatidic acid, phosphatidylglycerol, bis(dipalmitoylglycero)phosphate and their phosphono analogues were totally inactive. Similar data were obtained when platelet-rich plasma was used instead of washed rabbit platelets. Our results support the hypothesis that the effect of cardiolipin is mediated through specific paf receptors that act on the rabbit platelet membrane.
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