FSLLRY-NH2, a protease-activated receptor 2 (PAR2) antagonist, activates mas-related G protein-coupled receptor C11 (MrgprC11) to induce scratching behaviors in mice.

AIMS: Protease-activated receptor 2 (PAR2), a type of G protein-coupled receptor (GPCR), plays a significant role in pathophysiological conditions such as inflammation. A synthetic peptide SLIGRL-NH2 (SLIGRL) can activate PAR2, while FSLLRY-NH2 (FSLLRY) is an antagonist. A previous study showed that SLIGRL activates both PAR2 and mas-related G protein-coupled receptor C11 (MrgprC11), a different type of GPCR expressed in sensory neurons. However, the impact of FSLLRY on MrgprC11 and its human ortholog MRGPRX1 was not verified. Hence, the present study aims to verify the effect of FSLLRY on MrgprC11 and MRGPRX1. METHODS: The calcium imaging technique was applied to determine the effect of FSLLRY in HEK293T cells expressing MrgprC11/MRGPRX1 or dorsal root ganglia (DRG) neurons. Scratching behavior was also investigated in wild-type and PAR2 knockout mice after injecting FSLLRY. KEY FINDINGS: It was surprisingly discovered that FSLLRY specifically activates MrgprC11 in a dose-dependent manner, but not other MRGPR subtypes. Furthermore, FSLLRY also moderately activated MRGPRX1. FSLLRY stimulates downstream pathways including Gαq/11, phospholipase C, IP3 receptor, and TRPC ion channels to evoke an increase in the intracellular calcium levels. The molecular docking analysis predicted that FSLLRY interacts with the orthosteric binding pocket of MrgprC11 and MRGPRX1. Finally, FSLLRY activated primary cultures of mouse sensory neurons, and induced scratching behaviors in mice. SIGNIFICANCE: The present study has revealed that FSLLRY is capable of triggering itch sensation through activation of MrgprC11. This finding highlights the importance of considering the unexpected activation of MRGPRs in future therapeutic approaches aimed at the inhibition of PAR2.

Effects of household water-repellent agents and number of coating layers on the physical properties of cotton woven fabrics.

The increased interest in outdoor activities has prompted the demand for water-repellent fabrics that can withstand various environmental factors. In this study, the water repellency and physical properties, namely thickness, weight, tensile strength, elongation, and stiffness, of cotton woven fabrics were analyzed according to various treatments with different types of household water-repellent agents and number of coating layers. Fluorine-, silicone-, and wax-based water-repellent agents were coated on cotton woven fabrics once, thrice, and five times. Thickness, weight, and stiffness increased with the number of coating layers, which may reduce comfort. These properties increased minimally for the fluorine- and silicone-based water-repellent agents, whereas they considerably increased for the wax-based water-repellent agent. The fluorine-based water-repellent agent had a low water repellency rating of 2.2 even after five coating layers, and the silicone-based water-repellent agent had a higher rating of 3.4 with the same five coating layers. Meanwhile, the wax-based water-repellent agent had the highest water repellency rating of 5 even with only one coating layer, which was maintained with repeated coatings. Therefore, fluorine- and silicone-based water-repellent agents minimally altered the fabric properties even with repeated coatings; multiple coating layers, especially five or more layers for the fluorine-based water-repellent agent, are recommended to attain excellent water repellency. Conversely, one coating layer of the wax-based water-repellent agent is recommended to retain the comfort of the wearer.