Parkinson disease drug screening based on the interaction between D2 dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis

Zheng Zhou, Jun-Ming Liao, Peng Zhang, Jun-Bao Fan, Jie Chen, Yi Liang()

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Protein Cell ›› 2011, Vol. 2 ›› Issue (11) : 899-905. DOI: 10.1007/s13238-011-1096-0
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Parkinson disease drug screening based on the interaction between D2 dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis

  • Zheng Zhou, Jun-Ming Liao, Peng Zhang, Jun-Bao Fan, Jie Chen, Yi Liang()
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Abstract

Parkinson’s disease is the second most common neurodegenerative disease in the world. Beta-arrestin-2 has been reported to be an important protein involved in D2 dopamine receptor desensitization, which is essential to Parkinson’s disease. Moreover, the potential value of pharmacological inactivation of G protein-coupled receptor kinase or arrestin in the treatment of patients with Parkinson’s disease has recently been shown. We studied the interaction between D2 dopamine receptor and beta-arrestin-2 and the pharmacological regulation of chemical compounds on such interaction using capillary zone electrophoresis. The results from screening more than 40 compounds revealed three compounds that remarkably inhibit the beta-arrestin-2/D2 dopamine receptor interaction among them. These compounds are promising therapies for Parkinson’s disease, and the method used in this study has great potential for application in large-scale drug screening and evaluation.

Keywords

drug screening / D2 dopamine receptor / beta-arrestin-2 / capillary zone electrophoresis / protein-protein interaction / Parkinson’s disease

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Zheng Zhou, Jun-Ming Liao, Peng Zhang, Jun-Bao Fan, Jie Chen, Yi Liang. Parkinson disease drug screening based on the interaction between D2 dopamine receptor and beta-arrestin 2 detected by capillary zone electrophoresis. Prot Cell, 2011, 2(11): 899‒905 https://doi.org/10.1007/s13238-011-1096-0

References

[1] Andersen, P.H., Gingrich, J.A., Bates, M.D., Dearry, A., Falardeau, P., Senogles, S.E., and Caron, M.G. (1990). Dopamine receptor subtypes: beyond the D1/D2 classification. Trends Pharmacol Sci 11, 231–236 2200181.
[2] Calabresi, P., Mercuri, N.B., and Di Filippo, M. (2009). Synaptic plasticity, dopamine and Parkinson’s disease: one step ahead. Brain 132, 285–287 19168452.
[3] Dagher, A., and Robbins, T.W. (2009). Personality, addiction, dopamine: insights from Parkinson’s disease. Neuron 61, 502–510 19249271.
[4] DeWire, S.M., Ahn, S., Lefkowitz, R.J., and Shenoy, S.K. (2007). β-arrestins and cell signaling. Annu Rev Physiol 69, 483–510 17305471.
[5] Ding, L., Zhang, X.X., Wei, P., Fan, K., and Lai, L. (2005). The interaction between severe acute respiratory syndrome coronavirus 3C-like proteinase and a dimeric inhibitor by capillary electrophoresis. Anal Biochem 343, 159–165 15935325.
[6] Dodd, M.L., Klos, K.J., Bower, J.H., Geda, Y.E., Josephs, K.A., and Ahlskog, J.E. (2005). Pathological gambling caused by drugs used to treat Parkinson disease. Arch Neurol 62, 1377–1381 16009751.
[7] Dromey, J.R., and Pfleger, K.D. (2008). G protein coupled receptors as drug targets: the role of β-arrestins. Endocr Metab Immune Disord Drug Targets 8, 51–61 18393923.
[8] Emilien, G., Maloteaux, J.M., Geurts, M., Hoogenberg, K., and Cragg, S. (1999). Dopamine receptors—physiological understanding to therapeutic intervention potential. Pharmacol Ther 84, 133–156 10596903.
[9] Fahn, S., Oakes, D., Shoulson, I., Kieburtz, K., Rudolph, A., Lang, A., Olanow, C.W., Tanner, C., and Marek, K., and the Parkinson Study Group. (2004). Levodopa and the progression of Parkinson’s disease. N Engl J Med 351, 2498–2508 15590952.
[10] Gainetdinov, R.R., Premont, R.T., Bohn, L.M., Lefkowitz, R.J., and Caron, M.G. (2004). Desensitization of G protein-coupled receptors and neuronal functions. Annu Rev Neurosci 27, 107–144 15217328.
[11] García-Campa?a, A.M., Taverna, M., and Fabre, H. (2007). LIF detection of peptides and proteins in CE. Electrophoresis 28, 208–232 17136735.
[12] Goldman-Rakic, P.S., Castner, S.A., Svensson, T.H., Siever, L.J., and Williams, G.V. (2004). Targeting the dopamine D1 receptor in schizophrenia: insights for cognitive dysfunction. Psychopharmacology (Berl) 174, 3–16 15118803.
[13] Holzgrabe, U., Brinz, D., Kopec, S., Weber, C., and Bitar, Y. (2006). Why not using capillary electrophoresis in drug analysis? Electrophoresis 27, 2283–2292 16786478.
[14] Jankovic, J. (2008). Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 79, 368–376 18344392.
[15] Kelly, E., Bailey, C.P., and Henderson, G. (2008). Agonist-selective mechanisms of GPCR desensitization. Br J Pharmacol 153, S379–S388 18059321.
[16] Kobilka, B.K., and Deupi, X. (2007). Conformational complexity of G-protein-coupled receptors. Trends Pharmacol Sci 28, 397–406 17629961.
[17] Kostal, V., Katzenmeyer, J., and Arriaga, E.A. (2008). Capillary electrophoresis in bioanalysis. Anal Chem 80, 4533–4550 18484738.
[18] Lefkowitz, R.J., and Shenoy, S.K. (2005). Transduction of receptor signals by β-arrestins. Science 308, 512–517 15845844.
[19] Levoye, A., and Jockers, R. (2008). Alternative drug discovery approaches for orphan GPCRs. Drug Discov Today 13, 52–58 18190864.
[20] Ma, L., and Pei, G. (2007). b-arrestin signaling and regulation of transcription. J Cell Sci 120, 213–218 17215450.
[21] Macey, T.A., Gurevich, V.V., and Neve, K.A. (2004). Preferential Interaction between the dopamine D2 receptor and Arrestin2 in neostriatal neurons. Mol Pharmacol 66, 1635–1642 15361545.
[22] Mehler-Wex, C., Riederer, P., and Gerlach, M. (2006). Dopaminergic dysbalance in distinct basal ganglia neurocircuits: implications for the pathophysiology of Parkinson’s disease, schizophrenia and attention deficit hyperactivity disorder. Neurotox Res 10, 167–179 17197367.
[23] Neve, K.A., Seamans, J.K., and Trantham-Davidson, H. (2004). Dopamine receptor signaling. J Recept Signal Transduct Res 24, 165–205 15521361.
[24] Oakley, R.H., Laporte, S.A., Holt, J.A., Caron, M.G., and Barak, L.S. (2000). Differential affinities of visual arrestin, β arrestin1, and β arrestin2 for G protein-coupled receptors delineate two major classes of receptors. J Biol Chem 275, 17201–17210 10748214.
[25] Obeso, J.A., Marin, C., Rodriguez-Oroz, C., Blesa, J., Benitez-Temi?o, B., Mena-Segovia, J., Rodríguez, M., and Olanow, C.W. (2008). The basal ganglia in Parkinson’s disease: current concepts and unexplained observations. Ann Neurol 64, S30–S46 19127584.
[26] Olanow, C.W., Obeso, J.A., and Stocchi, F. (2006). Drug insight: Continuous dopaminergic stimulation in the treatment of Parkinson’s disease. Nat Clin Pract Neurol 2, 382–392 16932589.
[27] Premont, R.T., and Gainetdinov, R.R. (2007). Physiological roles of G protein-coupled receptor kinases and arrestins. Annu Rev Physiol 69, 511–534 17305472.
[28] Premont, R.T., Inglese, J., and Lefkowitz, R.J. (1995). Protein kinases that phosphorylate activated G protein-coupled receptors. FASEB J 9, 175–182 7781920.
[29] Reiter, E., and Lefkowitz, R.J. (2006). GRKs and β-arrestins: roles in receptor silencing, trafficking and signaling. Trends Endocrinol Metab 17, 159–165 16595179.
[30] Rosenbaum, D.M., Rasmussen, S.G., and Kobilka, B.K. (2009). The structure and function of G-protein-coupled receptors. Nature 459, 356–363 19458711.
[31] Savitt, J.M., Dawson, V.L., and Dawson, T.M. (2006). Diagnosis and treatment of Parkinson disease: molecules to medicine. J Clin Invest 116, 1744–1754 16823471.
[32] Skinbjerg, M., Ariano, M.A., Thorsell, A., Heilig, M., Halldin, C., Innis, R.B., and Sibley, D.R. (2009). Arrestin3 mediates D(2) dopamine receptor internalization. Synapse 63, 621–624 19309759.
[33] Whalen, E.J., Rajagopal, S., and Lefkowitz, R.J. (2011). Therapeutic potential of β-arrestin- and G protein-biased agonists. Trends Mol Med 17, 126–139 21183406.
[34] Wilson, C.J., and Copeland, R.A. (1997). Spectroscopic characterization of arrestin interactions with competitive ligands: study of heparin and phytic acid binding. J Protein Chem 16, 755–763 9365924.
[35] Xiao, K., Shenoy, S.K., Nobles, K., and Lefkowitz, R.J. (2004). Activation-dependent conformational changes in β-arrestin 2. J Biol Chem 279, 55744–55753 15501822.
[36] Yang, P., Whelan, R.J., Mao, Y., Lee, A.W., Carter-Su, C., and Kennedy, R.T. (2007). Multiplexed detection of protein-peptide interaction and inhibition using capillary electrophoresis. Anal Chem 79, 1690–1695 17297974.
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