Gennadi Kobzar

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.

Modulatory effect of 8-iso-PGE2 on platelets☆

1. 8-Iso-PGE2 induced either reversible or irreversible aggregation of platelets in human platelet-rich plasma (PRP) or in the suspension of washed platelets (WP). The values of EC50 for irreversible aggregation in PRP and WP were 4 and 2 microM, respectively. 2. In rabbit PRP, 8-iso-PGE2 (0.1-100 microM) itself did not induce or induced only reversible aggregation. 3. 8-Iso-PGE2 (0.1-20 microM) potentiated adenosine diphosphate-(ADP) induced platelet aggregation in both human and rabbit. The same effect also was found for adrenaline-induced platelet aggregation in rabbit. 4. The lower concentrations (0.2-0.5 microM) of 8-iso-PGE2 decreased, and higher concentrations (1-2 microM) increased platelet aggregating factor- (PAF) induced aggregation in human PRP. In rabbit PRP, 8-iso-PGE2 (0.02-200 microM) had only a decreasing effect on PAF-induced aggregation. 5. The results suggest that low concentrations of 8-iso-PGE2 can amplify or weaken platelet aggregation induced by various aggregatory agents.

Comparison of the inhibitory effect of E-prostaglandins in human and rabbit platelet-rich plasma and washed platelets

1. The anti-aggregatory potency of a number of E-type PGs was compared in human and rabbit platelet-rich plasma (PRP) and washed platelets. The potency of 13,14-dihydro-PGE1 and 5,6-dihydro-PGE3 is significantly higher in human than in rabbit washed platelets, while the potency of 15-keto-13,14-dihydro-PGE1 is higher in rabbit. 2. The potency of PGEs in rabbit PRP is very similar to that of washed platelets, with the exception of 1a,1b-dihomo-PGE2, which is of a significantly lower potency in PRR. 3. In human, 5,6-trans-PGE2, PGE3, and 15-keto-13,14-dihydro-PGE1 are more potent in PRP than in washed platelets. 4. The results indicate that the potency of E-type PGs in human and rabbit platelets is different and plasma can essentially influence the anti-aggregatory effect of PGEs; plasma can either decrease or increase potency.

Inhibition of platelet aggregation by pyridoxine

Abstract Vitamin B 6 in the form of pyridoxal-5′-phosphate (PLP) has been previously shown to inhibit in vitro platelet aggregation induced by several different agonists. However, this inhibitory effect took place only at millimolar concentrations of PLP that is too high to have physiological relevance. The aim of this work was to study the anti-aggregatory effect of vitamin B 6 in the form of pyridoxine (PN) hydrochloride. Experiments were performed on platelets separated from the human blood. Aggregation was measured photometrically. The values of PN HCl concentration causing 50% inhibition of ADP-induced platelet aggregation (IC 50 ) were obtained from concentration-effect curves. PN HCl inhibited platelet aggregation at low concentrations, IC 50 being 1.7 ± 0.5 μM. This indicates that the antiplatelet effect of PN HCl may have physiological relevance.

Blood plasma influences anti-aggregatory potency of prostaglandins: Effect of albumin

The anti-aggregatory effects of prostaglandins (PGs) were compared in platelet-rich plasma (PRP) with that in washed platelets (WP). PGE1, 13,14-dihydro-PGE1, 5,6-dihydro-PGE3 and ethyl ester of PGE1 had the same potency in both platelet preparations. Iloprost was significantly more potent in WP compared to PRP, while 5,6-trans-PGE2 and PGE3 had higher potency in PRP than in WP. Albumin (35 mg/ml) in WP decreased the potency of iloprost but did not change the IC50 value for PGE3. In PRP, PGs were 1.5–2.8 times more potent when incubated 3 min as compared to 30 s, while in WP, the incubation time did not affect the IC50 values for PGs. In WP with albumin, the potency of iloprost was significantly lower when it was incubated 30 s as compared to 3 min. Thus, plasma albumin is responsible for time-dependent effect of PGs and for the lower potency of iloprost but not for the higher potency of PGs in PRP.