PAR-4 Agonist Peptide, amide(AY-NH2) (PAR-4-AP; AY-NH2) 是一种蛋白酶激活的受体 4 (PAR-4) 激动剂，对 PAR-1 或 PAR- 均无影响2 并且其作用被 PAR-4 拮抗剂阻断。
AY-NH2 is a selective agonist of PAR4 with EC50 value of 11 μM [1].
Protease-activated receptor-4 (PAR4) is a member of PARs and plays an important role in mediating cellular effects of thrombin through acting G-proteins i, 12/13 (Rho and Ras activation) and q (calcium signaling) [2].
AY-NH2 is a potent PAR4 agonist and has a higher (~10 fold) activity than GYPGKF-NH2. Using rat platelet aggregation assay, it was shown that AY-NH2 had highly platelet aggregation ability than GY-NH2 and GF-NH2 [1]. When tested with platelet-rich plasma harvested from wild-type C57BL6 mice, AY-NH2 treatment exhibited highly agonist activity on PAR4 while had no effect on other PARs [3].
In male Wistar rats model of paw oedema, i.pl. injection of AY-NH2 markedly reduced the nociceptive score in response to both noxious and non-noxious mechanical stimuli, thus inhibiting carrageenan-induced mechanical hyperalgesia and allodynia [4].
参考文献:
[1].? Hollenberg, M.D., et al., Proteinase-activated receptor-4: evaluation of tethered ligand-derived peptides as probes for receptor function and as inflammatory agonists in vivo. Br J Pharmacol, 2004. 143(4): p. 443-54.
[2].? Yu, G., et al., Increased expression of protease-activated receptor 4 and Trefoil factor 2 in human colorectal cancer. PLoS One, 2015. 10(4): p. e0122678.
[3].? Faruqi, T.R., et al., Structure-function analysis of protease-activated receptor 4 tethered ligand peptides. Determinants of specificity and utility in assays of receptor function. J Biol Chem, 2000. 275(26): p. 19728-34.
[4].?? Asfaha, S., et al., Protease-activated receptor-4: a novel mechanism of inflammatory pain modulation. Br J Pharmacol, 2007. 150(2): p. 176-85.
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Animal experiment: |
Mice[1]SCID mice Male SCID mice and their BALB/cBy controls are operated as C57BL/6J mice, and on the 4th postoperative day mice receive intracolonically (IC) infusion of 100 μg PAR-4-AP or vehicle. Visceral pain measurements started 1 h following the end of infusion[1]. |
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参考文献: [1]. Annaházi A, et al. Proteinase-activated receptor-4 evoked colorectal analgesia in mice: an endogenously activatedfeed-back loop in visceral inflammatory pain. Neurogastroenterol Motil. 2012 Jan;24(1):76-85, e13. |
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