Comparison of anti-aggregatory effects of PGI2, PGI3 and iloprost on human and rabbit platelets.
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.
Kobzar
G
G
Department of Bioorganic Chemistry, Institute of Chemistry, Tallinn Technical University, 12618 Tallinn, Estonia. gen@chemnet.ee
Mardla
V
V
Järving
I
I
Samel
N
N
D000818:Animals; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D016285:Iloprost / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013045:Species Specificity
D010975:Platelet Aggregation Inhibitors; C034240:prostaglandin I3; D011464:Epoprostenol; D016285:Iloprost