Henriksen Ruth Ann, Hanks Vallere K
Department of Internal Medicine, Brody School of Medicine at East Carolina University, Greenville, NC 27858-4354, USA. henriksenr@ mail.ecu.edu
Arterioscler Thromb Vasc Biol. 2002 May 1;22(5):861-6. doi: 10.1161/01.atv.0000014742.56572.25.
Previous reports have indicated that thrombin-induced thromboxane production by human platelets occurs through two types of interaction between thrombin and the platelet surface. One of these interactions is with protease activated receptor(PAR)-1, the first identified thrombin receptor. These studies were undertaken to determine whether stimulation of PAR-4 also results in thromboxane production. The results show that treatment of washed human platelets with the PAR-4 agonist AYPGKF stimulates a maximum of 40% to 60% of the thromboxane produced by 100 nmol/L thrombin. Maximal thromboxane production requires approximately 1.0 mmol/L AYPGKF, despite the observation that maximal aggregation is produced by 45 micromol/L AYPGKF. Thromboxane produced by the combined stimulation of PAR-1 and PAR-4 is additive. Pretreatment of platelets with 45 micromol/L AYPGKF partially desensitizes thromboxane production in response to higher concentrations of AYPGKF and thrombin but not to stimulation by SFLLRN. PAR-4-induced stimulation is also significantly inhibited by 60 micromol/L genistein. It is concluded that activation through either PAR-1 or PAR-4 results in thromboxane production, but that stimulation of neither receptor alone produces thromboxane equivalent to that produced by 100 nmol/L thrombin. Thus, these findings demonstrate the presence of two pathways for thrombin-induced thromboxane production by platelets as proposed previously.
先前的报道指出，凝血酶诱导人血小板产生血栓素是通过凝血酶与血小板表面的两种相互作用实现的。其中一种相互作用是与蛋白酶激活受体（PAR）-1，即首个被鉴定出的凝血酶受体。开展这些研究是为了确定PAR-4的激活是否也会导致血栓素的产生。结果显示，用PAR-4激动剂AYPGKF处理洗涤后的人血小板，所刺激产生的血栓素最多为100 nmol/L凝血酶所产生血栓素的40%至60%。尽管观察到45 μmol/L AYPGKF可产生最大聚集，但最大血栓素生成需要约1.0 mmol/L AYPGKF。PAR-1和PAR-4联合刺激所产生的血栓素具有加和性。用45 μmol/L AYPGKF预处理血小板会使血小板对更高浓度的AYPGKF和凝血酶刺激产生的血栓素生成部分脱敏，但对SFLLRN刺激不产生脱敏。PAR-4诱导的刺激也会被60 μmol/L染料木黄酮显著抑制。得出的结论是，通过PAR-1或PAR-4激活都会导致血栓素生成，但单独刺激这两种受体所产生的血栓素都不等于100 nmol/L凝血酶所产生的血栓素。因此，这些发现证明了先前提出的凝血酶诱导血小板产生血栓素存在两条途径。
