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标题：The cleaved peptide of the thrombin receptor is a strong platelet agonist
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作者：Mark I. Furman ; Longbin Liu ; Stephen E. Benoit 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：6
页码：3082-3087
DOI：10.1073/pnas.95.6.3082
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Thrombin cleaves its G-protein-linked seven-transmembrane domain receptor, thereby releasing a 41-aa peptide and generating a new amino terminus that acts as a tethered ligand for the receptor. Peptides corresponding to the new amino terminal end of the proteolyzed seven-transmembrane domain thrombin receptor [TR42-55, SFLLRNPNDKYEPF, also known as TRAP (thrombin receptor-activating peptide)], previously have been demonstrated to activate the receptor. In this study, we demonstrate that the 41-aa cleaved peptide, TR1-41 (MGPRRLLLVAACFSLCGPLLSARTRARRPESKATNATLDPR) is a strong platelet agonist. TR1-41 induces platelet aggregation. In whole-blood flow cytometric studies, TR1-41 was shown to be more potent than TR42-55 and almost as potent as thrombin, as determined by the degree of increase in: (i) platelet surface expression of P-selectin (reflecting granule secretion); (ii) exposure of the fibrinogen binding site on the glycoprotein (GP) IIb-IIIa complex; and (iii) fibrinogen binding to the activated GPIIb-IIIa complex. As determined by experiments with inhibitors [prostaglandin I2, staurosporine, wortmannin, the endothelium-derived relaxing factor congener S-nitroso-N-acetylcysteine (SNAC), EDTA, EGTA, and genestein], and with Bernard-Soulier or Glanzmann's platelets, we demonstrated that TR1-41-induced platelet activation is: (i) inhibited by cyclic AMP; (ii) mediated by protein kinase C, phosphatidyl inositol-3-kinase, myosin light chain kinase, and intracellular protein tyrosine kinases; (iii) dependent on extracellular calcium; and (iv) independent of the GPIb-IX and GPIIb-IIIa complexes. TR1-41-induced platelet activation was synergistic with TR42-55. In summary, the cleaved peptide of the seven-transmembrane domain TR (TR1-41) is a strong platelet agonist.
关键词：flow cytometry ; platelet activation ; P-selectin ; glycoprotein IIb-IIIa