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

Molecular Nutrition & Food Research
Min PiLeigh D Quarles

Abstract

The molecular mechanisms whereby gallates in green tea exert metabolic effects are poorly understood. 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. GA and EGCG have offsetting agonist and antagonist eff...Continue Reading

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Citations

Feb 15, 2020·Basic & Clinical Pharmacology & Toxicology·Christinna V Jørgensen, Hans Bräuner-Osborne
Apr 24, 2018·PloS One·Min PiL Darryl Quarles
May 1, 2020·Scientific Reports·Min PiL Darryl Quarles
Jul 9, 2020·Scientific Reports·Min PiL Darryl Quarles
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Giulia D'ArrigoFrancesca Spyrakis
Apr 17, 2020·Biochimica Et Biophysica Acta. General Subjects·Apurba BhattaraiYinglong Miao
May 7, 2020·Protein and Peptide Letters·Luca De ToniCarlo Foresta
Jan 16, 2022·NPJ Science of Food·Naoki HaradaRyoichi Yamaji

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