НЕЙРОПЕПТИД ГАЛАНИН: РОЛЬ В РЕГУЛЯЦИИ БИОЛОГИЧЕСКИХ ФУНКЦИЙ ОРГАНИЗМА ЧЕЛОВЕКА В НОРМЕ И ПРИ ПАТОЛОГИИ

DOI: https://doi.org/10.29296/24999490-2018-03-01

Р.Г. Гатаулин, О.М. Веселова, кандидат биологических наук, О.И. Писаренко, доктор биологических наук ФГБУ «НМИЦ кардиологии» Минздрава России, Российская Федерация, 121552, Москва, 3-я Черепковская ул., д. 15А E-mail: [email protected]

Нейропептид галанин (Гал) определяется в центральной и периферической нервной системе, а также в других органах и тканях животных и человека. Широкий спектр его биологической активности связан с активацией или ингибированием специфических рецепторов – GalR1, GalR2 и GalR3. Однако роль галанинергической системы в регуляции жизненно важных защитных функций организма остается недостаточно исследованной. В настоящем обзоре рассматривается экспрессия Гал при физиологических и патофизиологических процессах, обсуждается его регуляторная роль в сердечно-сосудистой системе, при высвобождении проинсулина из β-клеток поджелудочной железы, участие в реакциях воспаления и пищевом поведении. Приведены экспериментальные данные, указывающие на возможность использования рецепторов Гал в качестве мишеней для коррекции кардиометаболических нарушений. Они свидетельствуют о том, что механизмы внутриклеточной защиты сердца от ишемического и реперфузионного стресса, которые используют Гал и его биоактивные фрагменты, могут быть практически значимым направлением в изучении биологических свойств этого пептида.
Ключевые слова: 
галанин, рецепторы галанина, сердечно-сосудистая система, артериальная гипертензия, ишемия миокарда, сахарный диабет, центральная нервная система
Для цитирования: 
Гатаулин Р.Г., Веселова О.М., Писаренко О.И. НЕЙРОПЕПТИД ГАЛАНИН: РОЛЬ В РЕГУЛЯЦИИ БИОЛОГИЧЕСКИХ ФУНКЦИЙ ОРГАНИЗМА ЧЕЛОВЕКА В НОРМЕ И ПРИ ПАТОЛОГИИ. Молекулярная медицина, 2018; (3): -https://doi.org/10.29296/24999490-2018-03-01

Список литературы: 
  1. Tatemoto K., A. Rokaeus H. Jornvall T.J., McDonald and V. Mutt. Galanin: A novel biologically active peptide from porcine intestine. FEBS Lett. 1983, 164. 124–8.
  2. Wang S., He C., Hashemi T., Bayne M. Cloning and expressional characterization of a novel galanin receptor. Identification of different pharmacophores within galanin for the three galanin receptor subtypes. J. Biol. Chem. 1997; 272 (51): 31949–52.
  3. Jacoby A.S., Hort Y.J., Constantinescu G., Shine J., Iismaa T.P. Critical role forGALR1 galanin receptor in galanin regulation of neuroendocrinefunction and seizure activity. Brain Res Mol. Brain Res. 2002; 107 (2): 195–200.
  4. Crawley J.N., Austin M.C., Fiske S.M., Martin B., Consolo S., Berthold M., Langel U., Fisone G., Bartfai T. Activity of centrally administered galanin fragments on stimulation of feeding behavior and on galanin receptor binding in the rat hypothalamus. J. Neurosci. 1990; 10 (11): 3695–700.
  5. Locker F., Lang A.A., Koller A., Lang R., Bianchini R., Kofler B. Galanin modulates human and murine neutrophil activation in vitro. Acta Physiol (Oxf). 2015; 213 (3): 595–602.
  6. Uehara T., Kanazawa T., Mizukami H., Uchibori R., Tsukahara T., Urabe M., Kume A., Misawa K., Carey T.E., Suzuki M., Ichimura K., Ozawa K. Novel anti-tumor mechanism of galanin receptor type 2 in head and neck squamous cell carcinoma cells. Cancer Sci. 2014; 105 (1): 72–80.
  7. Kanazawa T., Misawa K., Misawa Y., Maruta M., Uehara T., Kawada K., Nagatomo T., Ichimura K. Galanin receptor 2 utilizes distinct signaling pathways to suppress cell proliferation and induce apoptosis in HNSCC. Mol Med Rep. 2014; 10 (3): 1289–94.
  8. Mitsukawa K., Lu X., Bartfai T. Galanin, galanin receptors and drug targets. Cellular and Molecular Life Sciences June. 2008; 65 (12): 1796–805.
  9. Lang R., Gundlach A.L., Holmes F.E., Hobson S.A., Wynick D., Hökfelt T., Kofler B. Physiology, signaling, and pharmacology of galanin peptides and receptors: three decades of emerging diversity. Pharmacol Rev. 2015; 67 (1): 118–75.
  10. Amiranoff B., Lorinet A.M., Lagny-Pourmir I., Laburthe M. Mechanism of galanin-inhibited insulin release. Occurrence of a pertussis-toxin-sensitive inhibition of adenylate cyclase. Eur. J. Biochem. 1988; 177 (1): 147–52.
  11. Runesson J. Galanin receptor ligands. Licentiate thesis. Stockholm University 2009.
  12. Langel U., Land T., Bartfai T. Design of chimeric peptide ligands to galanin receptors and substance P receptors. Int. J. Pept Protein Res. 1992; 39 (6): 516–22.
  13. Mazarati A.M., Baldwin R.A., Shinmei S., Sankar R. In vivo interaction between serotonin and galanin receptors types 1 and 2 in the dorsal raphe: implication for limbic seizures. J. Neurochem. 2005; 95: 1495–503.
  14. Khoshbouei H., Cecchi M., Morilak D.A. Modulatory effects of galanin in the lateral bed nucleus of the stria terminalis on behavioral and neuroendocrine responses to acute stress. Neuropsychopharmacology. 2002; 27: 25–34.
  15. Mazarati A., Lu X., Kilk K., Langel U., Wasterlain C., Bartfai T. Galanin type 2 receptors regulate neuronal survival, susceptibility to seizures and seizure-induced neurogenesis in the dentate gyrus. Eur. J. Neurosci. 2004; 19: 3235–44.
  16. Quynh N.T., Islam S.M., Floren A., Bartfai T., Langel U., Ostenson C.G. (2005). Effects of galnon, a non-peptide galanin-receptor agonist, on insulin release from rat pancreatic islets. Biochem. Biophys. Res. Commun. 328: 213–20.
  17. Belloni A.S., Malendowicz L.K., Rucinski M., Guidolin D., Nussdorfer G.G. Galanin stimulates cortisol secretion from human adrenocortical cells through the activation of galanin receptor subtype 1 coupled to the adenylate cyclase-dependent signaling cascade. Int. J. Mol. Med. 2007; 20 (6): 859–64.
  18. Seta Y., Kataoka S., Toyono T., Toyoshima K. Expression of galanin and the galanin receptor in rat taste buds. Arch Histol Cytol. 2006; 69: 273–80.
  19. Melander T., Hokfelt T., Rokaeus Å. et al. Coexistence of galanin-like immunoreactivity with catecholamines, 5-hydroxytryptamine, GABA and neuropeptides in the rat CNS. J. Neurosci. 1986; 6: 3640–54.
  20. Shandra A.A., Godlevskii L.S., Vikhrestyuk S.L., Oleinik A.A. The influence of activation of the superior colliculi on convulsive activity during picrotoxin kindling. Neurosci Behav Physiol. 1993; 23 (6): 562–7.
  21. Seutin V., Verbanck P., Massotte L., Dresse A. Galanin decreases the activity of locus coeruleus neurons in vitro. Eur. J. Pharmacol. 1989; 164 (2): 373–6.
  22. Evans H., Baumgartner M. Shine J., Herzog H. Genomic organization and localization of the gene encoding human preprogalanin. Genomics. 1993; 18 (3): 473–7.
  23. Deecher D.C., Mash D.C., Staley J.K., Mufson E.J. Characterization and localization of galanin receptors in human entorhinal cortex. Regul Pept. 1998; 73 (3): 149–59.
  24. Li Y., Mei Z., Liu S., Wang T., Li H., Li X.X., Han S., Yang Y., Li J., Xu Z.D. Galanin Protects from Caspase-8/12-initiated Neuronal Apoptosis in the Ischemic Mouse Brain via GalR1. Aging Dis. 2017; 8 (1): 85–100.
  25. McKnight G.L., Karlsen A.E., Kowalyk S., Mathewes S.L., Sheppard P.O., O’Hara P.J., Taborsky G.L. Sequence of human galanin and its inhibition of glucose-stimulated insulin secretion from RIN cells. Diabetes. 1992; 41: 82–7.
  26. Adeghate E., Ponery A.S. Large reduction in the number of galaninimmunoreactive cells in pancreatic islets of diabetic rats. Neuroendocrinology. 2001; 13: 706–10.
  27. Legalkis I.N., Mantzouridis T., Mountokalakis T. Positive correlation of galanin with glucose in healthy volunteers during an oral glucose tolerance test. Horm Metab Res. 2007; 39: 53–5.
  28. Leto D., Saltiel A.R. Regulation of glucose transport by insulin: traffic control of GLUT4. Nat Rev Mol. Cell. Biol. 2012; 13: 383–96.
  29. Guo L., Shi M., Zhang L. et al. Galanin antagonist increases insulin resistance by reducing glucose transporter 4 effect in adipocytes of rats. Gen Comp Endocrinol. 2011; 173: 159–63.
  30. de Mazancourt P., Goldsmith P.K., Weinstein L.S. Inhibition of adenylate cyclase activity by galanin in rat insulinoma cells is mediated by the G-protein Gi3. Biochem J. 1994; 303 (2): 369–75.
  31. Ahrén B., Rorsman P., Berggren P.O. Galanin and the endocrine pancreas. FEBS Lett. 1988; 229 (2): 233–7.
  32. Diaz–Cabiale Z., Vela C., Razani H., Coveñas R., Fuxe K., Narváez J.A. Role of galanin and galanin (1–15) on central cardiovascular control. Neuropeptides. 2005, 39 (3): 185–90.
  33. Abbott S.B., Pilowsky P.M. Galanin microinjection into rostral ventrolateral medulla of the rat is hypotensive and attenuates sympathetic chemoreflex. Am. J. Physiol Regul Integr Comp Physiol. 2009; 296 (4): 1019–26.
  34. Narváez J.A., Diaz-Cabiale Z., Hedlund P.B., Aguirre J.A., Coveñas R., González-Barón S., Fuxe K. The galanin receptor antagonist M40 blocks the central cardiovascular actions of the galanin N-terminal fragment (1–15). Eur. J. Pharmacol. 2000; 399 (2–3): 197–203.
  35. Coelho E.F., Ferrari M.F., Maximino J.R., Chadi G., Fior-Chadi D.R. Decreases in the expression of CGRP and galanin mRNA in central and peripheral neurons related to the control of blood pressure following experimental hypertension in rats. Brain Res. Bull. 2004; 64: 59–66.
  36. Diaz-Cabiale Z., Narváez J.A., Yanaihara N., González-Barón S., Fuxe K. Galanin/alpha2-receptor interactions in central cardiovascular control. Neuropharmacology. 2000; 39 (8): 1377–85.
  37. Fang P., Yu M., Wan D., Zhang L., Han L., Shen Z., Shi M., Zhu Y., Zhang Z., Bo P. Regulatory effects of galanin system on development of several age-related chronic diseases. Exp Gerontol. 2017; 95: 88–97.
  38. Hedlund P.B., Aguirre J.A., Narvaez J.A., Fuxe K. Centrally coinjected galanin and a5-HT1A agonist act synergistically to produce vasodepressor responses in the rat, Eur. J. Pharmacol. 1991, 204:87–95.
  39. Diaz-Cabiale Z., Parrado C., Vela C., Coveñas R., Yanaihara N., Fuxe K., González-Barón S., Narváez J.A. Intracisternal galanin/angiotensin II interactions in central cardiovascular control. Regul Pept. 2005; 127 (1–3): 133–40.
  40. Herring N., Cranley J., Lokale M.N., Li D., Shanks J., Alston E.N., Girard B.M., Carter E, Parsons R.L., Habecker B.A., Paterson D.J. The cardiac sympathetic co-transmitter galanin reduces acetylcholine release and vagal bradycardia: Implications for neural control of cardiac excitability. J. Mol. Cell. Cardiol. 2012; 52 (3): 667–76.
  41. Ewert T.J, Gritman K.R., Bader M., Habecker B.A. Post-infarct cardiac sympathetic hyperactivity regulates galanin expression. Neurosci Lett. 2008; 436 (2): 163–6.
  42. Habecker B.A, Gritman K.R., Willison B.D., Van Winkle D.M. Myocardial infarction stimulates galanin expression in cardiac sympathetic neurons. Neuropeptides. 2005; 39 (2): 89–95.
  43. He B., Shi M., Zhang L., Li G., Zhang L., Shao H., Li J., Fang P., Ma Y., Shi Q., Sui Y. Beneficial effect of galanin on insulin sensitivity in muscle of type 2 diabetic rats. Physiol Behav. 2011; 103 (3–4): 284–9.
  44. Kocic I. The influence of the neuropeptide galanin on the contractility and the effective refractory period of guinea-pig heart papillary muscle under normoxic and hypoxic conditions. J. Pharm. Pharmacol. 1998; 50 (12): 1361–4.
  45. Lu X., Lundström L., Bartfai T. Galanin (2–11) binds to GalR3 in trans-fected cell lines: Limitations for pharmacological definition of receptor subtypes. Neuropeptides. 2005; 39: 165–7.
  46. Шульженко В.С., Серебрякова Л.И., Студнева И.М., Пелогейкина Ю.А., Веселова О.М., Молокоедов А.С., Овчинников М.В., Палькеева М.Е., Сидорова М.В., Писаренко О.И. Способность N-концевого фрагмента нейропептида галанина уменьшать ишемическое и реперфузионное повреждение сердца крысы. Кардиологический вестник. 2016; 11 (3): 12–21.
  47. [Shul’zhenko V.S., Serebrjakova L.I., Studneva I.M., Pelogejkina Ju.A., Veselova O.M., Molokoedov A.S., Ovchinnikov M.V., Pal’keeva M.E., Sidorova M.V., Pisarenko O.I. Ability of N-terminal fragment of neuropeptide galanin to attenuate ischemia and reperfusion injury of rat heart. Kardiologicheskij vestnik. 2016; 11 (3): 12–21 (in Russian)]
  48. Tian R., Abel E.D. Responses of GLUT4-deficient hearts to ischemia underscore the importance of glycolysis. Circulation. 2001; 103 (24): 2961–6.
  49. Timotin A., Pisarenko O., Sidorova M., Studneva I., Shulzhenko V., Palkeeva M., Serebryakova L., Molokoedov A., Veselova O., Cinato M., Tronchere H., Boal F., Kunduzova O. Myocardial protection from ischemia/reperfusion injury by exogenous galanin fragment. Oncotarget. 2017; 8 (13): 21241–52.
  50. Gataulin R., Pisarenko O., Sidorova M., Studneva I., Palkeeva M., Serebryakova L., Molokoedov A., Veselova O., Shulzhenko V. Protective effects of N-terminal galanin fragments in myocardial ischaemia/reperfusion injury. Cardiovascular Research. 2017, in press.