Multiple Tyrosine Metabolites Are GPR35 Agonists

Overview

Journal Sci Rep

Specialty Science

Date 2012 Apr 24

PMID 22523636

Citations 33

Authors

Huayun Deng

Haibei Hu

Ye Fang

Affiliations

Soon will be listed here.

Abstract

Both kynurenic acid and 2-acyl lysophosphatidic acid have been postulated to be the endogenous agonists of GPR35. However, controversy remains whether alternative endogenous agonists exist. The molecular targets accounted for many nongenomic actions of thyroid hormones are mostly unknown. Here we report the agonist activity of multiple tyrosine metabolites at the GPR35. Tyrosine metabolism intermediates that contain carboxylic acid and/or catechol functional groups were first selected. Whole cell dynamic mass redistribution (DMR) assays enabled by label-free optical biosensor were then used to characterize their agonist activity in native HT-29. Molecular assays including β-arrestin translocation, ERK phosphorylation and receptor internalization confirmed that GPR35 functions as a receptor for 5,6-dihydroxyindole-2-carboxylic acid, 3,3',5'-triiodothyronine, 3,3',5-triiodothyronine, gentisate, rosmarinate, and 3-nitrotyrosine. These results suggest that multiple tyrosine metabolites are alternative endogenous ligands of GPR35, and GPR35 may represent a druggable target for treating certain diseases associated with abnormality of tyrosine metabolism.

Citing Articles

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References

Wise A, Jupe S, Rees S . The identification of ligands at orphan G-protein coupled receptors. Annu Rev Pharmacol Toxicol. 2004; 44:43-66. DOI: 10.1146/annurev.pharmtox.44.101802.121419. View

Stathatos N, Daniels G . Autoimmune thyroid disease. Curr Opin Rheumatol. 2011; 24(1):70-5. DOI: 10.1097/BOR.0b013e32834ddb27. View

Wu S, Green W, Huang W, Hays M, Chopra I . Alternate pathways of thyroid hormone metabolism. Thyroid. 2005; 15(8):943-58. DOI: 10.1089/thy.2005.15.943. View

Fukuyama N, Takebayashi Y, Hida M, Ishida H, Ichimori K, Nakazawa H . Clinical evidence of peroxynitrite formation in chronic renal failure patients with septic shock. Free Radic Biol Med. 1997; 22(5):771-4. DOI: 10.1016/s0891-5849(96)00401-7. View

He W, Miao F, Lin D, Schwandner R, Wang Z, Gao J . Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature. 2004; 429(6988):188-93. DOI: 10.1038/nature02488. View

Petersen M, Abdullah Y, Benner J, Eberle D, Gehlen K, Hucherig S . Evolution of rosmarinic acid biosynthesis. Phytochemistry. 2009; 70(15-16):1663-79. DOI: 10.1016/j.phytochem.2009.05.010. View

Fang Y, Ferrie A . Label-free optical biosensor for ligand-directed functional selectivity acting on beta(2) adrenoceptor in living cells. FEBS Lett. 2008; 582(5):558-64. DOI: 10.1016/j.febslet.2008.01.021. View

Inoue H, Hisamatsu K, Ando K, Ajisaka R, Kumagai N . Determination of nitrotyrosine and related compounds in biological specimens by competitive enzyme immunoassay. Nitric Oxide. 2002; 7(1):11-7. DOI: 10.1016/s1089-8603(02)00005-8. View

Haynes D, Wright P, Gadd S, Whitehouse M, Vernon-Roberts B . Is aspirin a prodrug for antioxidant and cytokine-modulating oxymetabolites?. Agents Actions. 1993; 39(1-2):49-58. DOI: 10.1007/BF01975714. View

10.

Pacher P, Beckman J, Liaudet L . Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007; 87(1):315-424. PMC: 2248324. DOI: 10.1152/physrev.00029.2006. View

11.

Greenacre S, Ischiropoulos H . Tyrosine nitration: localisation, quantification, consequences for protein function and signal transduction. Free Radic Res. 2001; 34(6):541-81. DOI: 10.1080/10715760100300471. View

12.

Slominski A, Tobin D, Shibahara S, Wortsman J . Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev. 2004; 84(4):1155-228. DOI: 10.1152/physrev.00044.2003. View

13.

Nemirovskiy O, Radabaugh M, Aggarwal P, Funckes-Shippy C, Mnich S, Meyer D . Plasma 3-nitrotyrosine is a biomarker in animal models of arthritis: Pharmacological dissection of iNOS' role in disease. Nitric Oxide. 2009; 20(3):150-6. DOI: 10.1016/j.niox.2008.12.005. View

14.

Yang Y, Fu A, Wu X, Reagan J . GPR35 is a target of the loop diuretic drugs bumetanide and furosemide. Pharmacology. 2012; 89(1-2):13-7. DOI: 10.1159/000335127. View

15.

Slominski A, Zmijewski M, Pawelek J . L-tyrosine and L-dihydroxyphenylalanine as hormone-like regulators of melanocyte functions. Pigment Cell Melanoma Res. 2011; 25(1):14-27. PMC: 3242935. DOI: 10.1111/j.1755-148X.2011.00898.x. View

16.

Frost M, Halliwell B, Moore K . Analysis of free and protein-bound nitrotyrosine in human plasma by a gas chromatography/mass spectrometry method that avoids nitration artifacts. Biochem J. 2000; 345 Pt 3:453-8. PMC: 1220777. View

17.

Levitzki A, Mishani E . Tyrphostins and other tyrosine kinase inhibitors. Annu Rev Biochem. 2006; 75:93-109. DOI: 10.1146/annurev.biochem.75.103004.142657. View

18.

Taniguchi Y, Tonai-Kachi H, Shinjo K . Zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, is an agonist for GPR35. FEBS Lett. 2006; 580(21):5003-8. DOI: 10.1016/j.febslet.2006.08.015. View

19.

Klein I, Ojamaa K . Thyroid hormone and the cardiovascular system. N Engl J Med. 2001; 344(7):501-9. DOI: 10.1056/NEJM200102153440707. View

20.

Zhao P, Sharir H, Kapur A, Cowan A, Geller E, Adler M . Targeting of the orphan receptor GPR35 by pamoic acid: a potent activator of extracellular signal-regulated kinase and β-arrestin2 with antinociceptive activity. Mol Pharmacol. 2010; 78(4):560-8. PMC: 2981393. DOI: 10.1124/mol.110.066746. View