FSLLRY-NH2はプロテアーゼ活性化の受容体2(PAR-2)の拮抗剤である[1]。FSLLRY-NH2は、PAR-2の外部ループ2 (ECL-2) と結合することで、受容体の活性化を阻害し、よってプロテアーゼ誘発のシグナル伝導を遮断する[2]。FSLLRY-NH2は、炎症、掻痒と免疫反応の研究に使われる[3-4]。
HepG2細胞で、FSLLRY-NH2 (100-300μM; 24h)はSAPK/JNK経路を通じて、H2O2による炎症促進遺伝子IL-8、IL-1bとTNF-αのレベルを減らした[5]。A549細胞で、FSLLRY-NH2 (100μM; 24h)は細胞でPAR2発見を阻害する[6]。
窒息性心停止（ACA）誘発のラットモデルで、FSLLRY-NH2 (50µg；鼻内投与；単回投与)の処理は、ACA後、神経学的転帰を著しく改善し、変性海馬体ニューロンの数を減らした[7]。Ren-TGマウスで、FSLLRY-NH2 (10μg/kg；皮下；4週間)の処理は、PAR-2, β-MHC, COL3A1とGF-β1の総心臓mRNA発見の増加を軽減した[8]。
References:
[1]. Ocasio-Rivera M, Marin-Maldonado F, Trossi-Torres G, et al. Targeting of protease activator receptor-2 (PAR-2) antagonist FSLLRY-NH2 as an asthma adjuvant therapy[J]. Medicine, 2020, 99(43): e22351.
[2]. Hughes K H. Effects of chronic subcutaneous adminstered proteinase-activated receptor 2-activating peptide on vascular reactivity of aortas and blood pressures in mice[D]. Memorial University of Newfoundland, 2011.
[3]. Tsagareli M G, Follansbee T, Iodi Carstens M, et al. Targeting transient receptor potential (TRP) channels, Mas-related G-protein-coupled receptors (Mrgprs), and protease-activated receptors (PARs) to relieve itch[J]. Pharmaceuticals, 2023, 16(12): 1707.
[4]. Weng H J, Pham Q T T, Chang C W, et al. Druggable Targets and Compounds with Both Antinociceptive and Antipruritic Effects[J]. Pharmaceuticals, 2022, 15(7): 892.
[5]. Lee Y J, Kim S J, Kwon K W, et al. Inhibitory effect of FSLLRY-NH2 on inflammatory responses induced by hydrogen peroxide in HepG2 cells[J]. Archives of Pharmacal Research, 2017, 40(7): 854-863.
[6]. Wang B, Wu M D, Lan Y J, et al. PAR2 promotes malignancy in lung adenocarcinoma[J]. American Journal of Translational Research, 2024, 16(12): 7416.
[7]. Ocak U, Ocak P E, Huang L, et al. FSLLRY-NH2 improves neurological outcome after cardiac arrest in rats[J]. Turk Neurosurg, 2020, 30(2): 244-251.
[8]. Narita M, Hanada K, Yokono Y, et al. P938 A direct factor Xa inhibitor, rivaroxaban, attenuates cardiac hypertrophy and fibrosis in renin-overexpressing hypertensive mice[J]. European Heart Journal, 2018, 39(suppl_1): ehy564. P938.