Ex-orphan receptors as targets for potential medicines
Abstract
The orphan receptors are brought the review of modern literature on endogenous ligands of large group. It is shown that intermediates of carbohydrate, fatty and protein metabolism, a cycle the three-carbonic acids actively participate in regulation of exchange processes, and their synthetic analogs - ligands to orphan receptors (both agonist, and antagonists) are perspective objects of development new drugs at a wide range of diseases (diabetes, obesity, a metabolic syndrome, autoimmune diseases, a hypertensive illness, myocardium ischemia, a myocardium hypertrophy, neurodegenerative diseases, immunodeficiency, liver diseases, etc.). Concerning several ex-orphan receptors potentially perspective chemical compounds which can act as ligands to receptors of metabolic type of activation are presented.
About the Authors
E. B. Shustov
ФГБУН «Научный центр биомедицинских технологий ФМБА России», Московская область
Russian Federation
Russian Federation
S. V. Okovitiy
ГОУ ВПО «Санкт-Петербургская химико-фармацевтическая академия» Минздрава РФ, Санкт-Петербург
Russian Federation
Russian Federation
References
1. Апелин и дифференцировка эмбриональных стволовых клеток [Электронный ресурс]. - Режим доступа: http://surgeryzone.net/news/apelin-i-differencirovka-embrionalnyx-stvolovyx-kletok.html, свободный. - Загл. с экрана. - Яз. рус.
2. Беглен Д., Деманж Л., Мартине Ж., Мулен А., Перриссоуд Д., Ференц Ж-А. Способ лечения или профилактики физиологических и/или патофизиологических состояний, опосредуемых рецепторами, стимулирующими секрецию гормона роста, триазолы и фармацевтическая композиция на их основе. - Патент РФ 2415134.
3. Каркищенко Н.Н. Инновационные лекарства и нелетальные технологии XXI века // Биомедицина. 2006. № 3. С. 5-21.
4. Каркищенко Н.Н. Альтернативы биомедицины. Т. 2. Классика и альтернативы фармакотоксикологии. - М.: Изд-во ВПК. 2007. 448 с.
5. Оковитый С.В., Суханов Д.С., Заплутанов В.А., Смагина А.Н. Применение антигипоксантов в клинической практике [Электронный ресурс]. - Режим доступа: http://www.critical.ru/actual/IT/antihypo.htm, свободный. - Загл. с экрана. - Яз. рус.
6. Пелогейкина Ю.А. Регуляция метаболизма ишемизированного сердца структурными аналогами пептида апелина-12: Автореф. дисс.. канд. биол. наук. - М. 2015. 28 с.
7. Раевнева Т.Г., Артишевская Н.И., Савченко А.А. Цирротическая кардиомиопатия // Вестник Белорусского государственного медицинского университета. 2014. Вып. 6 «В помощь практикующему врачу». С. 119-124.
8. Сахарный диабет MODY-типа [Электронный ресурс]. - Режим доступа: http://medkarta.com/?cat=article&id=26225, свободный. - Загл. с экрана. - Яз. рус.
9. Стокигт Д.Р. Влияние лекарственных препаратов на функцию житовидной железы [Электронный ресурс]. - Режим доступа: http://bono-esse.ru/blizzard/A/Posobie/AFG/GVS/glandula_thyroidea_f_sostojanie_lab_ls.html, свободный. - Загл. с экрана. Яз. рус.
10. Aguiar C.J. Succinate causes pathological cardiomyocyte hypertrophy through GPR91 activation // Cell Communication and Signaling. 2014. №12:78 - DOI 10.1186/s12964-014-0078-2.
11. Ariza A.C., Meinardus P., Robben D., Robben J.H. The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions // Frontiers in endocrinology. 2012. V. 3. Art. 22.
12. Blad C.C., Tang C., Offermanns S. G protein-coupled receptors for energy metabolites as new therapeutic targets // Nature reviews - Drug discovery. 2012. V. 11. Р. 603-619.
13. Bomprezzi R. Dimethyl fumarate in the treatment of relapsing-remitting multiple sclerosis: an overview // Ther. Adv. Neurol. Disord. 2015. V. 8. № 1. DOI: 10.1177/1756285614564152.Р. 20-30.
14. Briscoe C.P. Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules // Br. J. Pharmacol. 2006. V. 148. P. 619-628.
15. Burness C.B., Deeks E.D. Dimethyl Fumarate: A review of its use in patients with relapsing-remitting multiple sclerosis // CNS Drugs. 2014. V. 28:373-387 DOI 10.1007/s40263-014-0155-5.
16. Center for drug evaluation and research: medical review(s), application number:204063orig1s000. 2013.
17. Chen H., Assmann J.C., Krenz A., Rahman M., Grimm M., Karsten C.M, Köhl J., Offermanns S., Wettschureck N., Schwaninger M. Hydroxycarboxylic acid receptor 2 mediates dimethyl fumarate’s protective effect in EAE // The J. of Clinical investigation. 2014. V. 124. N 5. P. 2188-2192.
18. Deen P.M.T., Robben J.H. Succinate Receptors in the Kidney // J. Am. Soc. Nephrol. 2011. V. 22. P. 1416-1422.
19. Feingold K.R., Moser A., Shigenaga J.K., Grunfeld C. Inflammation stimulates niacin receptor (GPR109A/HCA2) expression in adipose tissue and macrophages // J. of Lipid research. 2014. V. 55. P. 2501-2508.
20. Fu J. Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha // Nature. 2003. V. 411. Р. 284-293.
21. He W., Miao F.J.-P., Lin D.C.-H., Schwandner R.T., Wang Z., Gao J., Chen J.-L., Tian H., Ling L. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors // Nature. 2004. V. 429. Р. 188-193.
22. Högberg C., Gidlöf O., Tan C., Svensson S., Nilsson-Öhman J., Erlinge D., Olde B. Succinate independently stimulates full platelet activation via cAMP and phosphoinositide 3-kinase-β signaling // J. Thromb. Haemost. 2011. V. 9. № 2. P. 361-372. DOI 10.1111/j.1538-7836.2010.04158.x.
23. Liu C., Wu J., Zhu J., Kuei C., Yu J., Shelton J., Sutton S.W., Li X., Yun S.J., Mirzadegan T., Mazur C., Kamme F., Lovenberg T.W. Lactate Inhibits Lipolysis in Fat Cells through Activation of an Orphan G-protein-coupled Receptor, GPR81 // The J. of biological chemistry. 2009. V. 284. N. 5. P. 2811-2822.
24. Lukianova L.D. Current issues of adaptation to hypoxia. Signal mechanisms and their role in system regulation // Pathol. phiziol. exp. ter. 2011. V. 1. P. 3-19.
25. Oh D.Y. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects // Cell. 2010. V. 142. P. 687-698.
26. Peti-Peterdi J. High glucose and renin release: the role of succinate and GPR91 // Kidney Int. 2010. V. 78. № 12:1214-1217. DOI: 10.1038/ki.2010.333.
27. Peti-Peterdi J. Mitochondrial TCA cycle intermediates regulate body fluid and acid-base balance // J. Clin. invest. 2013; 123(7):2788-2790. DOI:10.1172/JCI68095.
28. Peti-Peterdi J., Gevorgyan H., Lam L., Riquier-Brison A. Metabolic control of renin secretion // Pflugers. Arch. 2013. V. 465. № 1:53-8. DOI: 10.1007/s00424-012-1130-y.
29. Rahman M., Muhammad S., Khan M., Chen H., Ridder D.A., Muёller-Fielitz H., Pokornaґ B., Vollbrandt T., Stoёlting I., Nadrowitz R., Okun J.G., Offermanns S., Schwaninger M. The b-hydroxybutyrate receptor HCA2 activates a neuroprotective subset of macrophages // Nature communications. 2014. V. 5. P. 3944. DOI: 10.1038/ncomms4944.
30. Robben J.H., Fenton R.A., Vargas S.L., Schweer H., Peti-Peterdi J., Deen P.M.T., Milligan G. Localization of the succinate receptor in the distal nephron and its signaling in polarized MDCK cells // Kidney International. 2009. V. 76. P. 1258-1267.
31. Roehrs C., Garrido-Sanabria E.R., Da Silva A.C., Faria L.C., Sinhorin V.D., Marques R.H., Priel M.R., Rubin M.A., Cavalheiro E.A., Mello C.F. Succinate increases neuronal post-synaptic excitatory potentials in vitro and induces convulsive behavior through N-methyl-d-aspartate-mediated mechanisms // Neuroscience. 2004. V. 125. № 4. P. 965-971.
32. Ruggieri S., Tortorella C., Gasperini C. Pharmacology and clinical efficacy of dimethyl fumarate (BG-12) for treatment of relapsing-remitting multiple sclerosis // Therapeutics and clinical risk management. 2014. V.10. P. 229-239.
33. Ryberg E. The orphan receptor GPR55 is a novel cannabinoid receptor // Br. J. Pharmacol. 2007. N 24. P. 116-127.
34. Smith N.J. Low affinity GPCRs for metabolic intermediates: challenges for pharmacologists // Frontiers in Endocrinology. 2012. V.3. № 1. Art.1. DOI: 10.3389.tendo.2012/00001.
35. Solt L.A., Banerjee S., Campbell S., Kamenecka T.M., Burris T.P. ROR inverse agonist suppresses insulitis and prevents hyperglycemia in a mouse model of type 1 diabetes // Endocrinology. 2015. V. 156. №3. P. 869-81. DOI: 10.1210/en.2014-1677.
36. Song F. Synthesis and biological evaluation of 3-aryl-3-(4-phenoxy)-propionic acid as a novel series of G protein-coupled receptor 40 agonists // J. Med. chem. 2007. V. 50. P. 2807-2817.
37. Steneberg P., Rubins N., Bartoov-Shifman R., Walker M.D., Edlund H. The FFA receptor GPR40 links hyperinsulinemia, hepatic steatosis, and impaired glucose homeostasis in mouse // Cell. Metab. 2005. V. 1. P. 245-258.
38. Stone V.M. The cytoprotective effects of oleoylethanolamide in insulin-secreting cells do not require activation of GPR119 // Br. J. Pharmacol. 2012. V. 110. P. 346-350.
39. Tan C.P. Selective small-molecule agonists of G protein-coupled receptor 40 promote glucose-dependent insulin secretion and reduce blood glucose in mice // Diabetes. 2008. V. 57. P. 2211-2219.
40. Tang H., Lu J.Y.-L., Zheng X., Yang Y., Reagan J.D. The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist // Biochemical and biophysical research communications. 2008. V. 375. P. 562-565.
41. Toma I., Kang J.J., Sipos A., Vargas S., Bansal E., Hanner F., Meer E., Peti-Peterdi J. Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney // The J. of Clinical investigation. 2008. V. 118. № 7. P. 2526-2534.
42. Tonack S., Tang C., Offermanns S. Endogenous metabolites as ligands for G protein-coupled receptors modulating risk factors for metabolic and cardiovascular disease // Am. J. Physiol. heart circ. physiol. 2013. V. 304. P. H501-H513.
43. Venci J.V., Gandhi M.A. Dimethyl fumarate (tecfidera): A new oral agent for multiple sclerosis // Annals of Pharmacotherapy. 2013. V. 47. № 12. P. 1697-1702.
44. Wang J., Simonavicius N., Wu X., Swaminath G., Reagan J., Tian H., Ling L. Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35 // J. Biol. chem. 2006. V. 281. № 31. P. 22021-22028. DOI: 10.1074/jbc.M603503200.
45. Yang L., Yu D., Fan H.-H., Feng Y., Hu L., Zhang W.-Y., Zhou K., Mo X.-M. Triggering the succinate receptor GPR91 enhances pressure overload-induced right ventricular hypertrophy // Int. J. Clin. exp. pathol. 2014. V. 7. № 9. P. 5415-5428.
46. Zheng J., Umikawa M., Cui C., Li J., Chen X., Zhang C., Hyunh H.D., Kang X., Silvany R., Wan X., Ye J., Cantó A.P., Chen S.-H., Wang H.-Y., Ward E.S., Zhang C.C. Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development // Nature. 2012. V. 485(7400). P. 656. DOI: 10.1038/nature11095.
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Shustov E.B., Okovitiy S.V. Ex-orphan receptors as targets for potential medicines. Journal Biomed. 2015;1(2):15-29. (In Russ.)
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