Involvement of Mas-related G protein-coupled receptor X1 (MrgprX1) in the chronic itch

Abstract

Atopic dermatitis (AD) is a common dermatologic disease that is accompanied by severe chronic pruritus. Recently, it has been reported that mas-related G protein-coupled receptor (Mrgpr) involves in the control of histamine-independent itch and the modulation of Mrgpr might be a promising target for the treatment of chronic itch. In the present study, we used the transgenic mice expressed human MrgprX1 in the sensory nerve and Mrgpr cluster KO (Mrgpr-KO) mice and evaluated the scratching behaviors in the acute itch model evoked by BAM8-22. In addition, the modulation of Mrgpr and the effect of steroid drug in the MC903-induced chronic itch model in both transgenic mice were examined. Intradermal BAM8-22 did not induce the scratching behaviors in the Mrgpr-KO mice over vehicle-treatment, on the other hand, it evoked scratching behaviors in the hMrgprX1 transgenic mice compared to the vehicle-treated animals. In the chronic itch model evoked by the repetitive application of MC903 produced the scratching behaviors in both Mrgpr-KO and hMrgprX1 transgenic mice over vehicle-treatment, but the ones in the hMrgprX1 mice evidently outweighed them in the Mrgpr-KO mice. In addition, dexamethasone, a steroid drug, significantly attenuated the scratching behaviors evoked by MC903 in both Mrgpr-KO and hMrgprX1 transgenic mice to the same extent. From these observations, it is suggested that the itch in the AD patients might be able to be inhibited completely by the combination of steroid and hMrgprX1 antagonist.