Protease-activated (thrombin) GPCR Assays
Background of PARs
Proteases play important roles in regulating cell apoptosis and survival. They communicate directly with cells through specific receptors called protease-activated receptors (PARs). PAR, is also known as the thrombin receptor. The PAR family has four members (PAR1-4), which are widely expressed in vivo and can be activated by a variety of proteases. PARs appear to be involved in platelet activation and coagulation as well as inflammatory responses.
Distribution and Functions of PARs
Different PARs have different distributions and functions. For example, the PAR1 receptor acts on platelets, neutrophils, smooth muscle cells, and neurons to promote a coordinated response to vascular injury. PAR2 is mainly expressed at vascular-rich sites, suggesting a role for this receptor in regulating vascular tone. PAR3 is widely distributed, for example, it is expressed in the heart, bone marrow, and vascular endothelium. PAR4 is mainly found in the lung, pancreas, thyroid, and testis.
Signaling of PARs
Most of the effects of PAR are mediated by Gᵢ, Gq, and G12/13, involving multiple signaling pathways.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| PAR1 | F2R |
|
|
|
| PAR2 | F2RL1 |
|
|
|
| PAR3 | F2RL2 |
|
||
| PAR4 | F2RL3 |
|
|
|
Assay List of Protease-activated (Thrombin) Receptors
Creative Biolabs can provide a range of assays of protease-activated (thrombin) receptors. You can choose the assay in the list or contact us for more information:
| Assay No. | Assay Name | Host Cell | Assay Type | Datasheet |
|---|---|---|---|---|
| Calcium Flux Assay | ||||
| S01YF-1122-KX843 | Magic™ Human F2RL2 In Vitro Calcium Flux Assay | CHO-K1 | Calcium Flux Assay | |
| Assay No. | Assay Name | Host Cell | Assay Type | Datasheet |
|---|---|---|---|---|
| Calcium Flux Assay | ||||
| S01YF-0722-KX187 | Magic™ Human F2RL3 In Vitro Calcium Assay, HEK293-Ga15 | HEK293-Ga15 | Calcium Assay | |
Published Data
| Paper Title | Nociceptive Sensitization by Activation of Protease-Activated Receptor 2 in a Rat Model of Incisional Pain |
| Journal | Brain Sciences |
| Published | 2021 |
| Abstract | Postoperative pain and subsequent inflammatory responses following tissue incision are detrimental to many surgical patients. This article sheds light on whether tryptase-induced activation of PAR2 triggers nociception and whether PAR2 antagonists have an effect on reducing the nociceptive response to nick in vivo and in vitro. The effect of preconditioning with the PAR2 antagonist ENMD-1068 on pain behavior was assessed following plantar incision in rats. The effects of the PAR2 agonist SLIGRL-NH2 on nociception were assessed following injection into the hind paw. In addition, the response of C mechanosensitive nociceptors to PAR2 agonists was also observed using an in vitro skin-neural preparation. This article revealed that PAR2 may support early nociception after incision by sensitizing rat C fibers directly or indirectly. Furthermore, PAR2 may be involved in the early modulation of postoperative pain along with other co-factors that contribute to postoperative pain. |
| Result |
This article found that blocking PAR2 with ENMD-1068 was effective in transiently reducing incision-induced protective pain and thermal hypersensitivity, highlighting the critical role of peripheral PAR2 in early incision pain. Furthermore, preventing mast cell degranulation was highly effective in reducing postoperative hyperalgesia in mice. Importantly, this article suggested that PAR2-activated nociception on primary afferents leading to spontaneous activity might facilitate thermal and mechanical responses by central sensitization, or that PAR2-activated nociception may depend on other circulating molecules that influenced sensory neuron excitability.
|
Fig.1. Effects of PAR2 antagonist ENMD 1068 on pain behaviors of rats after incision. (Kido, 2021)
Reference
- Kido, K.; et al. Nociceptive Sensitization by Activation of Protease-Activated Receptor 2 in a Rat Model of Incisional Pain. Brain Sciences. 2021; 11(2): 144.
