Hollenberg M D, Saifeddine M
Department of Pharmacology & Therapeutics, The University of Calgary, Faculty of Medicine, AB, Canada.
Can J Physiol Pharmacol. 2001 May;79(5):439-42.
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.
我们在大鼠血小板聚集试验中研究了受体激活肽类似物（PAR4APs）的作用，这些类似物是以小鼠蛋白酶激活受体-4（PAR4）经蛋白水解后暴露的拴系配体序列为模型设计的。PAR4APs GYPGKF-NH2（GY-NH2）和AYPGKF-NH2（AY-NH2）能够引起聚集，其半数有效浓度（EC50）值分别约为40微摩尔和15微摩尔。人PAR4反向序列（VQGPYG-NH2，YG-NH2）和PAR1AP SFLLR-NH2不会引起聚集。相比之下，反式肉桂酰-YPGKF-NH2（tcY-NH2）不会引起聚集，但能阻断由GY-NH2、AY-NH2和凝血酶引起的聚集，而不影响ADP介导的聚集。我们得出结论，与PAR1AP不同，PAR4APs GY-NH2和AY-NH2通过PAR4相关受体激活大鼠血小板，并且以PAR4拴系激活序列为模型设计的肽类似物可作为有用的激动剂和拮抗剂探针，用于评估在大鼠组织制剂中由PAR4APs或凝血酶激活PAR4的后果。
