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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 816159, 9 pages
http://dx.doi.org/10.1155/2012/816159
Research Article

Identification of Physiologically Active Substances as Novel Ligands for MRGPRD

1Exploratory Research Laboratories II, Daiichi Sankyo Co., Ltd., Tokyo 134-8630, Japan
2Biologics Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo 134-8630, Japan
3Oncology Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan
4Department of Chemical Biology, Gunma University Graduate School of Engineering, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515, Japan
5Institute for Biomolecular Science, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Tokyo 171-8588, Japan

Received 22 December 2011; Revised 6 April 2012; Accepted 5 May 2012

Academic Editor: S. L. Mowbray

Copyright © 2012 Makiko Uno et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.