首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Proteinase-activated receptor 4 (PAR4): activation and inhibition of rat platelet aggregation by PAR4-derived peptides.
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Proteinase-activated receptor 4 (PAR4): activation and inhibition of rat platelet aggregation by PAR4-derived peptides.

机译:蛋白酶激活受体4(PAR4):PAR4衍生的肽激活和抑制大鼠血小板聚集。

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摘要

We studied the actions of receptor-activating peptide analogues (PAR4APs), modeled on the proteolytically-revealed tethered ligand sequence of murine proteinase-activated receptor-4 (PAR4), in a rat platelet aggregation assay. The PAR4APs GYPGKF-NH2 (GY-NH2) and AYPGKF-NH2 (AY-NH2) were able to cause aggregation with EC50 values of about 40 microM and 15 microM, respectively. The reverse human PAR4 sequence (VQGPYG-NH2, YG-NH2) and the PAR1AP SFLLR-NH2, did not cause aggregation. In contrast, trans-cinnamoyl-YPGKF-NH2 (tcY-NH2) did not cause aggregation but blocked aggregation caused by GY-NH2, AY-NH2, and thrombin without affecting ADP-mediated aggregation. We conclude that in contrast to the PAR1AP, the PAR4APs GY-NH2 and AY-NH2 activate rat platelets via a PAR4-related receptor and that peptide analogues modeled on the PAR4 tethered activating sequence can serve as useful agonist and antagonist probes for assessing the consequence of activating PAR4 either by PAR4APs or thrombin in rat tissue preparations.
机译:我们在大鼠血小板凝集试验中研究了鼠蛋白酶激活受体4(PAR4)的蛋白水解揭示的拴系配体序列,模拟了受体激活肽类似物(PAR4APs)的作用。 PAR4AP GYPGKF-NH2(GY-NH2)和AYPGKF-NH2(AY-NH2)能够引起EC50值分别约为40 microM和15 microM的聚集。反向的人PAR4序列(VQGPYG-NH2,YG-NH2)和PAR1AP SFLLR-NH2没有引起聚集。相反,反式肉桂酰基-YPGKF-NH2(tcY-NH2)不会引起聚集,但会阻止由GY-NH2,AY-NH2和凝血酶引起的聚集,而不会影响ADP介导的聚集。我们得出的结论是,与PAR1AP相比,PAR4APs GY-NH2和AY-NH2通过PAR4相关受体激活大鼠血小板,在PAR4拴系激活序列上模拟的肽类似物可以用作评估结果的有用的激动剂和拮抗剂探针大鼠组织制剂中PAR4APs或凝血酶激活PAR4的作用。

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