Key result
PGI3 was as effective as PGI2 in inhibiting human platelet aggregation, but on rabbit platelets, the IC50 for PGI3 (10.2 nM) was twofold higher than that of PGI2.
Why the study?
Does PGI3 inhibit ADP-induced platelet aggregation differently than PGI2 and iloprost in human versus rabbit platelets?
Does PGI3 inhibit ADP-induced platelet aggregation differently than PGI2 and iloprost in human versus rabbit platelets?
PGI3 is as effective as PGI2 in inhibiting human platelet aggregation, but less potent in rabbit platelets, indicating pharmacological differences in prostacyclin receptors between species.
Caution against extrapolating rabbit platelet data to humans for PGI3; leaves open species-specific prostacyclin receptor pharmacology for targeted study.
In human, prostaglandin I3 (PGI3) is as potent inhibitor of platelet aggregation as prostacyclin (PGI2). However the data on the anti-aggregatiory effect of this prostaglandin is scanty on human and is absent on platelets of other species. The potency of PGI3 on other species may be different if there are differences in the structure of receptors. Comparison of the rank orders of the potency of the selective agonists in different species may provide evidence for the existence of such differences. The aim of this work was to study the anti-aggregatory effect of PGI3 on the platelets of human and rabbit and compare the rank orders of the potency of PGI2, PGI3, and iloprost, a synthetic analogue of PGI2, on the platelets of the two species. Experiments were performed in the suspensions of washed platelets prepared from the blood anticoagulated with trisodium citrate solution. A prostaglandin concentration causing 50% inhibition of ADP-induced platelet aggregation (IC50) was obtained from concentration-effect curves. On human platelets, PGI3 was as effective as PGI2, while on rabbit platelets, the value of IC50 for PGI3 (10.2 +/- 1.6 nM) was twofold higher than that of PGI2. The rank orders of agonist potency are different in rabbit compared to those of human. This indicates that the prostacyclin receptors of rabbit platelets are pharmacologically different from those of human.
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Kobzar et al. (2001) studied this question. PGI3 vs. PGI2 and iloprost was evaluated on 50% inhibition of ADP-induced platelet aggregation (IC50). PGI3 was as effective as PGI2 in inhibiting human platelet aggregation, but on rabbit platelets, the IC50 for PGI3 (10.2 nM) was twofold higher than that of PGI2.
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