FSLLRY-NH2, a protease-activated receptor 2 (PAR2) antagonist, activates mas-related G protein-coupled receptor C11 (MrgprC11) to induce scratching behaviors in mice
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Hye In | - |
dc.contributor.author | Lee, Gi Baek | - |
dc.contributor.author | Song, Da Eun | - |
dc.contributor.author | Sanjel, Babina | - |
dc.contributor.author | Lee, Wook-Joo | - |
dc.contributor.author | Shim, Won-Sik | - |
dc.date.accessioned | 2023-06-09T08:40:07Z | - |
dc.date.available | 2023-06-09T08:40:07Z | - |
dc.date.created | 2023-06-09 | - |
dc.date.issued | 2023-07 | - |
dc.identifier.issn | 0024-3205 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/88032 | - |
dc.description.abstract | 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 investi-gated 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 G alpha q/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. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | - |
dc.relation.isPartOf | Life Sciences | - |
dc.title | FSLLRY-NH2, a protease-activated receptor 2 (PAR2) antagonist, activates mas-related G protein-coupled receptor C11 (MrgprC11) to induce scratching behaviors in mice | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 001001216400001 | - |
dc.identifier.doi | 10.1016/j.lfs.2023.121786 | - |
dc.identifier.bibliographicCitation | Life Sciences, v.325 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85159612351 | - |
dc.citation.title | Life Sciences | - |
dc.citation.volume | 325 | - |
dc.contributor.affiliatedAuthor | Kim, Hye In | - |
dc.contributor.affiliatedAuthor | Lee, Gi Baek | - |
dc.contributor.affiliatedAuthor | Song, Da Eun | - |
dc.contributor.affiliatedAuthor | Sanjel, Babina | - |
dc.contributor.affiliatedAuthor | Lee, Wook-Joo | - |
dc.contributor.affiliatedAuthor | Shim, Won-Sik | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | FSLLRY | - |
dc.subject.keywordAuthor | MrgprC11 | - |
dc.subject.keywordAuthor | MRGPRX1 | - |
dc.subject.keywordAuthor | PAR2 | - |
dc.subject.keywordAuthor | Itch | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, Republic of Korea(13120)031-750-5114
COPYRIGHT 2020 Gachon University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.