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    CMUR > China Medical University Hospital > Jurnal articles >  Item 310903500/30515
    Please use this identifier to cite or link to this item: http://ir.cmu.edu.tw/ir/handle/310903500/30515


    Title: Gene frequencies of the HPA-1 to HPA-8w platelet antigen alleles in Taiwanese, Indonesian, and Thai
    Authors: Liu, TC;Shih, MC;Lin, CL;Lin, SF;Chen, CM;Chang, JG
    Contributors: 附設醫院醫研部;China Med Coll Hosp, Dept Lab Med, Taichung, Taiwan;China Med Coll Hosp, Dept Med Res, Taichung, Taiwan;Kaohsiung Med Univ Hosp, Div Hematooncol, Dept Med, Kaohsiung, Taiwan
    Date: 2002
    Issue Date: 2010-09-24 14:56:51 (UTC+8)
    Publisher: SPRINGER-VERLAG
    Abstract: In the present study, the antiplatelet effect and its mechanism of a new synthetic compound YD-3 [1-benzyl-3-(ethoxycarbonylphenyl)indazole] were examined. YD-3 inhibited the aggregation of washed human platelets caused by protease-activated receptor (PAR) 4 agonist peptide GYPGKF (IC50 = 0.13 +/- 0.02 muM), but had no or little effect on that by thrombin, PAR1 agonist peptide SFLLRN, collagen or U46619. YD-3 produced a parallel, rightward shift of the concentration-response curve for GYPGKF without decreasing of the maximum platelet aggregation, indicating a competitive antagonism. In contrast to human platelets, both thrombin- and GYPGKF-induced mouse platelet shape change and aggregation were completely inhibited by YD-3. YD-3 also selectively prevented GYPGKF-induced intracellular Ca2+ mobilization in human platelets. Furthermore, in the PAR1-desensitized human platelets. thrombin induced a relatively slow rise and decay of calcium mobilization that was significantly inhibited by YD-3. In addition, the synergistic effect of SFLLRN and GYPGKF on platelet activation was prevented by YD-3. YD-3 also inhibits both fMLP-stimulated neutrophil- and purified cathepsin G-induced platelet aggregation, which has been demonstrated to be PAR4-dependent. Taken together, our results suggest that YD-3 selectively inhibits PAR4-dependent platelet activation through blockade of PAR4. To the best of our knowledge, it is the first non-peptide PAR4 antagonist.
    Relation: ANNALS OF HEMATOLOGY 81(5):244-248
    Appears in Collections:[China Medical University Hospital] Jurnal articles

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