Proteinase-activated receptors (PARs) represent a unique subclass of G-protein-coupled receptors of which four family members have now been cloned from a number of species[3]. PAR1 has been implicated as a key mediator in cellular functions and is activated by the PAR1 agonist, thrombin, as well as by serine proteases. TRAP-6 is a PAR1 agonist[2]. Adenosine 5′-diphosphate (ADP) inducible aggregation which is used to assess platelet response to thienopyridines was correlated to that by TRAP-6 (r = 0.33 to 0.72; p < 0.001 for all assays)[4]. In platelet-rich plasma (PRP) of patients (n = 34) with unexplained venous thromboembolism, platelet aggregometry was performed and the influence of TRAP-6 was determined. Compared to the control group, patients with venous thromboembolism showed an enhanced maximal platelet aggregation with low concentrations of TRAP-6 (2 μM)[5].
TRAP-6 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human pulmonary artery endothelial cells (HPAECs)
50 ng/ml
2 hours
To investigate the effect of TRAP-6 on endothelial barrier function under mechanical stretch and PC treatment. Results showed that TRAP-6 exacerbated stretch-induced barrier disruption, while PC enhanced barrier protection via a KRIT1-dependent mechanism.
Am J Respir Cell Mol Biol. 2015 Dec;53(6):834-43.
HESC-derived platelets
40 μM
To evaluate the in vitro functionality of hESC-derived platelets upon stimulation with ADP and TRAP-6
Stem Cell Res Ther. 2024 Nov 28;15(1):454.
Human platelets
10 μmol/l
30 minutes
To evaluate the effect of dapagliflozin on platelet CD62P expression, results showed dapagliflozin reduced the percentage of CD62P-positive platelets after TRAP-6 stimulation.
Diabetologia. 2021 Aug;64(8):1834-1849.
TRAP-6 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
Two-hit model of ALI caused by high tidal volume mechanical ventilation and TRAP6 injection
Intratracheal injection
1.5 × 10−5 mol/kg
Single injection, lasting 4 hours
To investigate the effect of TRAP-6 on lung vascular permeability under high tidal volume mechanical ventilation. Results showed that TRAP-6 exacerbated lung vascular leak and injury, and KRIT1 deficiency further enhanced these effects and attenuated the protective effects of PC.
Am J Respir Cell Mol Biol. 2015 Dec;53(6):834-43.
Mice
Crescentic glomerulonephritis model
Subcutaneous injection
2 mg/kg
Twice daily for 10 days
To evaluate the effect of TRAP-6 on glomerular inflammation and injury via PAR-1 activation. Results showed that TRAP-6 significantly increased glomerular crescent formation, fibrin deposition, and inflammatory cell infiltration, indicating that PAR-1 activation exacerbates glomerular inflammation and injury.
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