GPCR6A Is a Molecular Target for the Natural Products Gallate and EGCG in Green Tea

Pi, Min; Kapoor, Karan; Ye, Ruisong; Smith, Jeremy C.; Baudry, Jerome; Quarles, Leigh D.

doi:10.1002/mnfr.201700770

Title: GPCR6A Is a Molecular Target for the Natural Products Gallate and EGCG in Green Tea

Journal Article · Wed Feb 21 00:00:00 EST 2018 · Molecular Nutrition & Food Research

DOI:https://doi.org/10.1002/mnfr.201700770· OSTI ID:1459287

Pi, Min ^[1]; Kapoor, Karan ^[2]; Ye, Ruisong ^[1]; Smith, Jeremy C. ^[3]; Baudry, Jerome ^[3]; Quarles, Leigh D. ^[1]

Univ. of Tennessee Health Science Center, Memphis, TN (United States). Dept. of Medicine
Univ. of Tennessee, Knoxville, TN (United States). UT/ORNL Center for Molecular Biophysics
Univ. of Tennessee, Knoxville, TN (United States). UT/ORNL Center for Molecular Biophysics and Dept. of Biochemistry and Cellular and Molecular Biology

1 Scope: The molecular mechanisms whereby gallates in green tea exert metabolic effects are poorly understood.2 Methods and results: We found that GPRC6A, a multi-ligand-sensing G-protein-coupled receptor that regulates energy metabolism, sex hormone production, and prostate cancer progression, is a target for gallates. Sodium gallate (SG), gallic acid (GA) > ethyl gallate (EG) > octyl gallate (OG) dose dependently activated ERK in HEK-293 cells transfected with GPRC6A but not in non-transfected controls. SG also stimulated insulin secretion in β-cells isolated from wild-type mice similar to the endogenous GPRC6A ligands, osteocalcin (Ocn) and testosterone (T). Side-chain additions to create OG resulted in loss of GPRC6A agonist activity. Another component of green tea, epigallocatechin 3-gallate (EGCG), dose-dependently inhibited Ocn activation of GPRC6A in HEK-293 cells transfected with GPRC6A and blocked the effect of Ocn in stimulating glucose production in CH10T1/2 cells. Using structural models of the venus fly trap (VFT) and 7-transmembrane (7-TM) domains of GPRC6A, calculations suggest that l-amino acids and GA bind to the VFT, whereas EGCG is calculated to bind to sites in both the VFT and 7-TM.3 In conclusion, GA and EGCG have offsetting agonist and antagonist effects on GPRC6A that may account for the variable metabolic effect of green tea consumption.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1459287

Journal Information:: Molecular Nutrition & Food Research, Vol. 62, Issue 8; ISSN 1613-4125

Country of Publication:: United States

Language:: English

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Cited by: 20 works

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59 BASIC BIOLOGICAL SCIENCES
computational modeling
EGCG
gallic acid
GPCR
GPRC6A

Title: GPCR6A Is a Molecular Target for the Natural Products Gallate and EGCG in Green Tea

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