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Relief of loperamide-induced constipation by peptidic and small molecule RXFP4 agonists in mice

文献类型：期刊论文

作者Yan, Shiyu1,2,4; Chen, Yan7,8; Wang, Jiang6; Wang, Qiuying5; Zhou, Qingtong7,8; Liu, Hong3; Wang, Ming-Wei7,8,9,10; Yang, Dehua1,2,4,5,9
刊名BIOCHEMICAL PHARMACOLOGY
出版日期2025-07-01
卷号237页码:12
关键词RXFP4 INSL5 Agonist Constipation Colonic motility
ISSN号0006-2952
DOI10.1016/j.bcp.2025.116924
英文摘要Constipation is a common gastrointestinal disorder often treated symptomatically as the existing therapies all have significant side-effects. The relaxin/insulin-like family peptide receptor 4 (RXFP4), a class A G protein-coupled receptor, has emerged as a potential drug target for this indication as it regulates intestinal motility. Here, we investigated the therapeutic effects of both peptidic (insulin-like peptide 5, INSL5) and small molecule (DC591053) RXFP4 agonists on loperamide-induced constipation in mice. Fecal water content, fecal weight, colonic transit time, and serum levels of neurotransmitters such as nitric oxide (NO), serotonin (5-HT), and vasoactive intestinal peptide (VIP) were assessed, in conjunction with the examination of colon tissue histology and expression levels of aquaporin 3 (AQP3), transient receptor potential vanilloid 1 (TRPV1), and calcitonin gene-related peptide (CGRP). It was found that both INSL5 and DC591053 dose-dependently increased fecal water content and weight, accelerated colonic transit, and improved colon morphology in constipated mice, accompanied by the altered expression levels of factors related to constipation. Comparative analysis revealed that while the two agonists produced similar beneficial outcomes, their different chemical nature may affect pharmacokinetics property and receptor engagement. Our results suggest that the activation of RXFP4 presents a novel approach to alleviating constipation.
WOS关键词CELL-LINES ; COLON ; IDENTIFICATION ; EXPRESSION ; SEROTONIN ; INSL5
资助项目Strategic Priority Research Program of the Chinese Academy of Sciences[XDB1060402] ; National Key Basic Research Program of China[2023YFA1800804] ; National Key Basic Research Program of China[2021ZD0203400] ; Hainan Provincial Major Science and Technology Project[ZDKJ2021028] ; Program of Shanghai Academic/Technology Research Leader[23XD1400900]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001469480400001
出版者PERGAMON-ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/317491]  
专题新药研究国家重点实验室
通讯作者Liu, Hong; Wang, Ming-Wei; Yang, Dehua
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Stake Key Lab Chem Biol, Shanghai 201203, Peoples R China
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
6.Lingang Lab, Shanghai 200031, Peoples R China
7.Shanghai Jiao Tong Univ, Res Ctr Med Struct Biol, Natl Res Ctr Translat Med Shanghai, State Key Lab Med Genom,Ruijin Hosp,Sch Med, Shanghai 200025, Peoples R China
8.Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai 200032, Peoples R China
9.Res Ctr Deepsea Bioresources, Sanya 572025, Hainan, Peoples R China
10.Hainan Med Univ, Engn Res Ctr Trop Med Innovat & Transformat, Sch Pharm, Minist Educ, Haikou 570228, Peoples R China
推荐引用方式
GB/T 7714		 Yan, Shiyu,Chen, Yan,Wang, Jiang,et al. Relief of loperamide-induced constipation by peptidic and small molecule RXFP4 agonists in mice[J]. BIOCHEMICAL PHARMACOLOGY,2025,237:12.
APA Yan, Shiyu.,Chen, Yan.,Wang, Jiang.,Wang, Qiuying.,Zhou, Qingtong.,...&Yang, Dehua.(2025).Relief of loperamide-induced constipation by peptidic and small molecule RXFP4 agonists in mice.BIOCHEMICAL PHARMACOLOGY,237,12.
MLA Yan, Shiyu,et al."Relief of loperamide-induced constipation by peptidic and small molecule RXFP4 agonists in mice".BIOCHEMICAL PHARMACOLOGY 237(2025):12.

入库方式： OAI收割

来源：上海药物研究所

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