Discovery of exogenous ligands for orphan receptor BRS-3 from Chinese herbs.
10.19540/j.cnki.cjcmm.20201112.201
- Author:
Xin QIU
1
;
Le-Hao WU
1
;
Yang YU
1
;
Yu JIN
2
;
Ji-Xia WANG
3
;
Chao-Ran WANG
3
;
Yan ZHANG
1
Author Information
1. School of Pharmacy, Shanghai Jiao Tong University Shanghai 200240, China.
2. School of Pharmacy, East China University of Science and Technology Shanghai 200237, China.
3. Dalian Institute of Chemical Physics, Chinese Academy of Sciences Dalian 116023, China DICP-CMC Innovation Institute of Medicine Taizhou 225300, China.
- Publication Type:Journal Article
- Keywords:
Chinese herbal monomers;
antagonist;
bombesin receptor subtype-3(BRS-3);
calcium current;
ligand;
orphan receptor
- MeSH:
Drugs, Chinese Herbal/chemistry*;
HEK293 Cells;
Humans;
Ligands;
Receptors, Bombesin
- From:
China Journal of Chinese Materia Medica
2022;47(6):1595-1602
- CountryChina
- Language:Chinese
-
Abstract:
Bombesin receptor subtype-3(BRS-3) is an orphan receptor in the bombesin receptor family. Its signal transduction mechanism and biological function have attracted much attention. Seeking the ligand for BRS-3 is of great significance for exploring its function. Considering the fact that the activation of BRS-3 receptor can induce the change in intracellular Ca~(2+) concentration, the fluo-rometric imaging plate reader(FLIPR) was utilized for ligand screening at the cellular level. Among more than 400 monomeric compounds isolated from Chinese herbs, yuanhunine from Corydalis Rhizoma and sophoraisoflavanone A and licoriphenone from Glycyrrhizae Radix et Rhizoma antagonized BRS-3 to varying degrees. It was confirmed in HEK293 cells expressing BRS-3 that yuanhunine, sophoraisoflavanone A, and licoriphenone inhibited the calcium current response after the activation of BRS-3 by [D-Phe~6,β-Ala~(11),Phe~(13),Nle~(14)]bombesin-(6-14) in a dose-dependent manner with the IC_(50) values being 8.58, 4.10, and 2.04 μmol·L~(-1), respectively. Further study indicated that yuanhunine and sophoraisoflavanone A exhibited good selectivity for BRS-3. In this study, it was found for the first time that monomers derived from Chinese herbs had antagonistic activity against orphan receptor BRS-3, which has provided a tool for further study of BRS-3 and also the potential lead compounds for new drug discovery. At the same time, it provides reference for the research and development of innovative drugs based on the active ingredients of Chinese herbs.
