title: Identification of physiologically active substances as novel ligands for MRGPRD.
abstract: Mas-related G-protein coupled receptor member D (MRGPRD) is a G protein-coupled receptor (GPCR) which belongs to the Mas-related GPCRs expressed in the dorsal root ganglia (DRG). In this study, we investigated two novel ligands in addition to beta-alanine: (1) beta-aminoisobutyric acid, a physiologically active substance, with which possible relation to tumors has been seen together with beta-alanine; (2) diethylstilbestrol, a synthetic estrogen hormone. In addition to the novel ligands, we found that transfection of MRGPRD leads fibroblast cells to form spheroids, which would be related to oncogenicity. To understand the MRGPRD novel character, oncogenicity, a large chemical library was screened in order to obtain MRGPRD antagonists to utilize in exploring the character. The antagonist in turn inhibited the spheroid proliferation that is dependent on MRGPRD signaling as well as MRGPRD signals activated by beta-alanine. The antagonist, a small-molecule compound we found in this study, is a potential anticancer agent.
authors.affiliation: Exploratory Research Laboratories II, Daiichi Sankyo Co, Ltd, Tokyo 134-8630, Japan. uno.makiko.mv@daiichisankyo.co.jp
authors.forename: Makiko
authors.initials: M
authors.lastname: Uno
authors.forename: Satoko
authors.initials: S
authors.lastname: Nishimura
authors.forename: Keisuke
authors.initials: K
authors.lastname: Fukuchi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kaneta
authors.forename: Yoko
authors.initials: Y
authors.lastname: Oda
authors.forename: Hironobu
authors.initials: H
authors.lastname: Komori
authors.forename: Shigeki
authors.initials: S
authors.lastname: Takeda
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Haga
authors.forename: Toshinori
authors.initials: T
authors.lastname: Agatsuma
authors.forename: Futoshi
authors.initials: F
authors.lastname: Nara
mesh_terms: D000621:Aminoisobutyric Acids / Q000737:chemistry*; D000818:Animals; D001665:Binding Sites; D004054:Diethylstilbestrol / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D051379:Mice; D041681:NIH 3T3 Cells; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000166:cytology* / Q000378:metabolism*; D015091:beta-Alanine / Q000737:chemistry*
chemical_list: D000621:Aminoisobutyric Acids; D008024:Ligands; C497098:Mrgprd protein, mouse; D043562:Receptors, G-Protein-Coupled; D015091:beta-Alanine; D004054:Diethylstilbestrol; C033435:3-aminoisobutyric acid