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      저자 : Huma Rasheed (검색결과 2 건)
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        Involvement of throm boxane A2 and tyrosine kinase in the synergistic interaction of platelet activating factor and calcium ionophore A23187 in human platelet aggregation

        Huma Rasheed,Sheikh Arshad Saeed 생화학분자생물학회 2004 Experimental and molecular medicine Vol.36 No.3

        The present study was caried out to examine the mechanisms of the synergistic interaction of PAF and A23187 mediated platelet aggregation. We found that platelet aggregation mediated by subthreshold concentrations of PAF (5 nM) and A23187 (1 M) was inhibited by PAF receptor blocker (WEB 2086, IC50 = 0 . 6 5 M) and calcium chanel blockers, diltiazem (IC50 = 1 3 M) and verapamil (IC50 = 1 8 M). Pretreatment of plate-lets with PAF and A23187 induced rise in in-blocked by verapamil. While examing the role of the down stream signaling pathways, we found that platelet aggregation induced by the co-adition of PAF and A23187 was also inhi-bited by low concentrations of phospholipase C (PLC) inhibitor (U7312; IC50 = 10 M), a cyclo-oxygenase inhibitor (indomethacin; IC50 = 0 . 2 M) and inhibitor of TLCK, herbimycin A with IC50 value of 5 M. The efect was also inhibited by a specific TXA2 receptor antagonist, SQ 29548 with very low IC50 value of 0.05 M. However, the inhibitors of MAP kinase, PD98059 and pro-tein kinase C, chelerythrine had no effect on PAF and A23187-induced platelet aggregation. These data sugest that the synergism between PAF and A23187 in platelet aggregation involves activa-tion of thromboxane and tyrosine kinase pathways.

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        Investigation of Piperidine Derivatives in Ex Vivo Models of Pain and Platelet Aggregation

        Zafar Saeed Saify,Huma Rasheed,Nousheen Mushtaq,Mehrun Nisa,Shazia Haider,Afshan Naz,Kaniz Fizza Azhar,Ghulam Abbas Miana 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.11

        Piperidine derivatives are known to exhibit analgesic activities and are likely to possess the ability to block the effects of prostaglandins through inhibition of downstream signaling pathways. The present study investigated the activity of five derivatives (PD2-6) of 4-(4'-bromophenyl)-4-piperidinol (PD1), against pain and platelet aggregation mediated by the release of prostaglandins and thromboxane A2, respectively. The results showed that compound PD1and its two phenacyl derivatives PD3 and PD5 exhibited a highly significant analgesic effect (p < 0.01), whereas PD4 and PD6 also showed significant activity. PD3, the most active analgesic compound when docked to the opioid receptor, had interactions between the oxygen of its nitro group and the amino group of ARG 573, indicating a distance of 1.2563 Å. The antiplatelet data showed that compound PD5 (4-(4'-bromo-phenyl)-4-hydroxy-1-[2-(2'',4''-dimethoxyphenyl)-2-oxo-ethyl]-piperidinium bromide) had an IC50 = 0.06 mM, which was the most active compound, whereas PD3 was the second most active compound against platelet aggregating factor-induced aggregation with an IC50 = 80 mM. Acetyl salicylic acid (IC50 = 150 μM) was used as a positive control.

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