Identification of a Novel Small-Molecule Agonist for Human G Protein-Coupled Receptor 3

doi:10.1124/jpet.114.213082.

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	Identification of a Novel Small-Molecule Agonist for Human G Protein-Coupled Receptor 3
	Ye, Chenli 2; Zhang, Zhenghong 2; Wang, Zhilong 1; Hua, Qiuhong 2; Zhang, Ru 2; Xie, Xin1,2
刊名	JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
	2014-06
卷号	349 期号:3 页码:437-443
ISSN号	0022-3565
DOI	10.1124/jpet.114.213082.
文献子类	Article
英文摘要	G protein-coupled receptor 3 (GPR3) is an orphan G protein-coupled receptor (GPCR) predominantly expressed in mammalian brain and oocytes. GPR3 plays important roles in these two organs and is known as a G alpha(s)-coupled receptor-activated constitutively in cells. However, the signal transduction pathway and pharmacological function of GPR3 remain unclear because of the lack of a specific ligand. By use of a human embryonic kidney 293 cell line stably expressing FLAG-GPR3-green fluorescent protein, a chemical screening for GPR3 ligands was performed using homogeneous time-resolved fluorescence cAMP assay. Diphenyleneiodonium chloride (DPI) was identified as a novel agonist of GPR3 with weak or no cross-reactivity with other GPCRs. DPI was further characterized to activate several GPR3-mediated signal transduction pathways, including Ca2+ mobilization, cAMP accumulation, membrane recruitment of beta-arrestin2, and receptor desensitization. Parallel studies revealed that the activity of DPI is much more pronounced than sphingosine 1-phosphate, a previously reported GPR3 agonist. Our study identified a novel and specific agonist of GPR3, which provides a useful tool for further study of this orphan GPCR.
资助项目	Ministry of Science and Technology of China[2014CB965002] ; Ministry of Science and Technology of China[2013ZX09507001] ; Ministry of Science and Technology of China[2012CB910406] ; Shanghai Commission of Science and Technology[12XD1402100]
WOS关键词	PREMATURE OVARIAN FAILURE ; MEIOTIC ARREST ; SPHINGOSINE 1-PHOSPHATE ; GPR3 ; EXPRESSION ; OOCYTES ; LIGAND ; TRANSDUCTION ; GENERATION ; INHIBITORS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
WOS记录号	WOS:000336156200008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277055]
专题	国家新药筛选中心
通讯作者	Zhang, Ru
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Natl Ctr Drug Screening, Shanghai 200031, Peoples R China 2.Tongji Univ, Sch Life Sci & Technol, Shanghai Key Lab Signaling & Dis Res, Lab Receptor Based Biomed, Shanghai 200092, Peoples R China;
推荐引用方式 GB/T 7714	Ye, Chenli,Zhang, Zhenghong,Wang, Zhilong,et al. Identification of a Novel Small-Molecule Agonist for Human G Protein-Coupled Receptor 3[J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,2014,349(3):437-443.
APA	Ye, Chenli,Zhang, Zhenghong,Wang, Zhilong,Hua, Qiuhong,Zhang, Ru,&Xie, Xin.(2014).Identification of a Novel Small-Molecule Agonist for Human G Protein-Coupled Receptor 3.JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,349(3),437-443.
MLA	Ye, Chenli,et al."Identification of a Novel Small-Molecule Agonist for Human G Protein-Coupled Receptor 3".JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 349.3(2014):437-443.