Клиническая медицина №3 2009

Рахимова О. Ю.

Мелатонин и его место в развитии заболеваний желудочно-кишечного тракта  

Изучение роли и использования мелатонина при лечении различных заболеваний представляет большой интерес на современном этапе. Мелатонин является гормоном, обладающим уникальными адаптивными возможностями, нарушение продукции и ритма выработки которого является пусковым механизмом развития десинхроноза и в дальнейшем органической патологии. Снижение его секреции отмечается при бессоннице, у лиц с заболеваниями сердечно-сосудистой системы, желудочно-кишечного тракта и сопровождает сезонные обострения хронических заболеваний, кроме того, обнаруживается при гормонально-зависимых опухолях. Понимание роли мелатонина в патогенезе различных заболеваний позволит использовать его для лечения целого ряда болезней.

Ключевые слова:  эпифизарные гормоны, мелатонин, колоректальный рак, APUD-клетки кишечника, десинхроноз

ЛИТЕРАТУРА
1. Коваленко Р. И. Нейроэндокринные «органы» головного мозга позвоночных. 1. Эпифиз. В кн.: Поленов А. Л. (ред.). Нейроэндокринология. Ч. 1, кн. вторая: Основы современной физиологии. СПб.; 1993. 300—324.
2. Хелимский А. М. Эпифиз (шишковидная железа). М.: Медицина; 1969.
3. Vollrath L. The pineal organ. In: Oksche A., Vollrath L., eds. Handbuch der mikroskopischen Anatomie des Menschen. Berlin; New York: Springer-Verlag; 1981; Vol. IV, Pt 10.
4. Петров С. В. Ультраструктурная характеристика нейросекреции в эпифизе мыши. В кн.: Волкова И. Н. (ред.) Вопросы нейробиологии: Науч. труды Казан. гос. мед. ин-та. Т. 68. Казань; 1987. 32—37.
5. Yu H.-S., Reiter R. J., eds. Melatonin. Biosynthesis, physiological effects, and clincal applications. Boca Raton, FL: CRC Press; 1993.
6. Korf H. W., Schomerus C., Stehle J. H. The pineal organ, its hormone melatonin, and the photoneuroendocrine system. Adv. Anat. Embryol. Cell Biol. 1998; 146: 1—100.
7. Arendt J. Melatonin and mammalian pineal gland. London: Chapman & Hall; 1995.
8. Sack R. L., Lewy A. J., Blood M. L. et al. Melatonin administration to blind people: phase advances and entrainment. J. Biol. Rhythms 1991; 6: 249—261.
9. Lewy A. J., Ahmed S., Jackson M. L., Sack R. L. Melatonin shifts human circadian rhythms according to a phase — response curve. Chronobiol. Int. 1992; 9: 380—392.
10. Cimino M., Vantini G., Algeri S. et al. Age-related modification of dopaminergic receptor system: restoration to normal activity by modifying membrane fluidity with S-adenosylmethionine. Life Sci. 1984; 34: 2029—2039.
11. Чазов Е. И., Исаченков В. А. Эпифиз: место и роль в системе нейроэндокринной регуляции. М.: Медицина; 1974.
12. Reiter R. J. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr. Rev. 1991; 12: 151—180.
13. Бондаренко Л. А. Современные представления о физиологии эпифиза. Нейрофизиология 1997; 29: 121—137.
14. Galliani I., Frank F. et al. Histochemical and ultrastructural study of the human pineal gland in the course of aging. J. Submicrosc. Cytol. Pathol. 1989; 21: 571—578.
15. Tuitou Y. Human aging and melatonin. Clinical relevance. Exp. Gerontol. 2001; 36: 1083—1100.
16. Tuitou Y., Bogdan A., Haus E., Tuitou C., Modifications of circadian and circannual rhythms with age. Exp. Gerontol. 1997; 32: 603—614.
17. Cope F. W. On the relativity and uncertainty of electromagnetic energy measurement at a superconductive boundary. Application to perception of weak magnetic fields by living systems. Physiol. Chem. Phys. 1981; 13: 231—239.
18. Tenforde T. S., Kaune W. T. Interaction of extremely low freguency electric and magnetic fields with humans. Hlth Phys. 1987; 53: 585—606.
19. Kavaliers M., Ossenkopp K. P. Calcium channel involvement in magnetic fields inhibition of morphine induced analgesia. Naunyn-Schmiedeberg’s Arch. Pharmacol. 1987; 336: 308—315.
20. Wehr T. A. A «clock for all seasons» in the human brain. Progr. Brain Res. 1996; 111: 321—342.
21. Bartsch H., Bartsch C. et al. The relationship between the pineal gland and cancer; seasonal aspects. In. Wetterberg L., eds. Light and biological rhythms in man. New York: Pergamon Press; 1993. 337—350.
22. Banerjee S., Margulis L. Mitotic arrest by melatonin. Exp. Cell Res. 1973; 78: 314—318.
23. Reiter R. J. The pineal and int hormones in the control of reproduction in mammals. Endocr. Rev. 1980; 1: 109—131.
24. Maestroni G., Conti A. The melatonin-immune system-opiod network. In: Advances in pineal research. London; 1990; vol. 4: 233—241.
25. Arendt J. Human responses to light and melatonin. In: Advances in pineal research. London; 1994; vol. 8: 439—441.
26. Pearse A. G. E. The cytochemistry and ultrastructure of polypeptide hormoneproducing cell of the APUD series and the embryologic and pathologic implications of the concept. J. Histochem. Cytochem. 1969; 17: 303—313.
27. Andrew A. The APUD concept: where has it led us? Br. Med. Bull. 1982; 38: 221—225.
28. Райхлин Н. Т., Кветной И. М., Осадчук М. А. APUD-система (общепатологические и онкологические аспекты). Обнинск; 1993.
29. Raikhlin N. T., Kvetnoy I. M. The APUD system (diffuse endocrine system) in normal and pathological states. Physiol. Gen. Biol. Rev. 1994; 8: 1—44.
30. Polak J. M., Bloom S. R. Immunocytochemistry of the diffuse neuroendocrine system. In: Immunocytochemistry: modern methods and applications. Bristol; 1986. 328—348.
31. Sundler F. et al. The neuroendocrine system of the gut. Acta Oncol. 1989; 283: 303—314.
32. Larsson L.-I. On the possible existence of multiple endocrine, paracrine and neurocrine messengers in secretory system. Invest. Cell Pathol. 1980; 3: 73—85.
33. Kvetnoy I. M., Sandvik A. K., Waldum H. L. The diffuse neuroendocrine system and extrapineal melatonin. J. Mol. Endocrinol. 1997; 18: 1—3.
34. Ozaki Y., Lynch H. Prensece of melatonin in plasma and urina of pinealectomised rats. Endocrinology 1976; 99: 641—644.
35. Kennaway D. J., Frith R. G. et al. A specific radioimmunoassay for melatonin in biological tissue and fluids and its validation by gas chromatography-mass spectrometry. Endocrinology 1977; 100: 2186—2194.
36. Erspamer V., Asero B. Identificaition of enteramine, the specific hormone of the enterochromaffine cell system, as 5-hydroxytryptamine. Nature 1952; 169: 800—801.
37. Barter R., Pearse A. G. E. Mammalian enterochromaffine cell as the source of serotonin (5-hydroxytryptamine). J. Pathol. Bacteriol. 1955; 69: 25—31.
38. Raikhlin N. T., Kvetnoy I. M., Tolkachev V. N. Melatonin may be synthesised in enterochromaffine cell. Nature 1975; 155: 344—345.
39. Raikhlin N. T., Kvetnoy I. M. Melatonin and enterochromaffine cell. Acta Histochem. 1976; 55: 19—25.
40. Lee P. P., Pang S. F. Melatonin and its reseptors in the gastrointestinal tract. Biol. Signals. 1993; 2: 181—193.
41. Кветной И. М. APUD-система (структурно-функциональная организация, биологическое значение в норме и патологии). Успехи физиол. наук 1987; 18: 84—102.
42. Huether G., Poeggeler B., Blanke J. et al. Effects of indirectly acting 5-HT receptor agonists on circulating melatonin in rats. Eur. J. Pharmacol. 1993; 238: 249—254.
43. Vialli M. Histology of the enterochromaffin cell. In: 5-Hydroxytryptamine and related indolealkylamines: handbook of experimental pharmacology. Berlin; 1966; vol. 19: 1—65.
44. Verhofstad A. A. J. et al. Immunocytochemical localization of noradrenaline and serotonin. In: Immunocytochemistry. Practical applications in biology and pathology. Bristol; 1983. 143—168.
45. Solcia E., Usellini L. et al. Endocrin cell producing regulatory peptides. In: Regulatory peptides. Basel; 1989. 220—246.
46. Kvetnoy I. M., Yuzhakov V. V. Extrapineal melatonin: advances in microscopical identification of hormones in endocrine and non-endocrine cells. Microscopy & Analysis 1993; 21: 27—29.
47. Pardridge W. M., Mietus L. J. Transport of albumin-bound melatonin through blood brain barrier. J. Neurochem. 1980; 34: 1761—1763.
48. Reiter R. J. Melatonin: that ubiquitously acting pineal hormonel. New Physiol. Sci. 1991; 6: 223—228.
49. Bubenik G. A. et al. Diurnal variation and binding characteristics of melatonin in the mouse brain and gastrointestinal tissues. Comp. Biochem. Physiol. C. 1993; 104. 221—224.
50. Rice J., Mayor J. et al. Effect of light therapy on salivary melatonin in seasonal affective disorder. J. Psychiatr. Res. 1995; 56. 221—228.
51. Bubenik G. A., Pang S. F., Hacker R. R., Smith P. S. Melatonin concentration in serum and tissues of porcine gastrointestinal tract and their relationship to the intake and passage of food. J. Pineal Res. 1996; 21: 251—256.
52. Huether G., Hajak G. et al. The metabolic fate of infused L-tryptophan in men: possible clinical implications of the accumulation of circulating tryptophan and tryptophan metabolites. Psychopharmacology 1992; 106: 422—432.
53. Yaga K., Reiter R. J. Tryptophan loading increases daytime serum melatonin in intact and pinealectomized rats. Life Sci. 1993; 52: 1231—1238.
54. Kvetnoy I. M., Yuzhakov V. V. Extrapineal melatonin nontraditional localization and possible significance for oncology. In: Advances in pineal research. London; 1994; vol. 7: 199—212.
55. Kvetnoy I. M., Kvetnaya T. V., Konopljannikov A. G. et al. Melatonin and proliferative activity of tumor growth: from experiments to clinical application In: Kvetnoy I. M., Reiter R. J., eds. Melatonin: general biological and oncoradiological aspects. Obninsk: MRRC Press; 1994. 17—23.
56. Осадчук М. А., Киричук В. Ф., Кветной И. М. Диффузная нейроэндокринная система: общепатологические и гастроэнтерологические аспекты. Саратов: Изд-во Саратов. ун-та; 1996.
57. Sagar S. M., Singh G., Hodson I. et al. Nitric oxide and anticancer therapy. Cancer Treat. Rev. 1995; 21: 159—181.
58. Kvetnoy I. M., Bartsch C., Bartsch H. et al. Melatonin and proliferative activity of tumours: successful combination of immunohistochemical and radioimmunological methods for definition of prognosis in humans. Acta Histochem. Cytochem. 1996; 29: 304—305.
59. Bartsch C., Kvetnoy I. M., Kvetnaya T. V. et al. Nocturnal urinary 6-sulphatoxymelatonin and proliferative cell nuclear antigen — immunopositive tumor cells show strong positive correlations in patients with gastrointestinal and lung cancer. J. Pineal Res. 1997; 23: 90—96.
60. Fioretti M. C., Menconi E., Riccardi C. Study on the type of antiserotoninergic antagonism exerted in vitro on rats stomach by pineal indole derivates. Farmacol Ed. Sci 1976; 29: 401—412.
61. Bubenik G. A. The effect of serotonin, N-acetylserotonin and melatonin on spontaneous contractions of isolated rat intestine. J. Pineal Res. 1986; 3: 42—54.
62. Harlow H. J., Weekly B. L. Effect of melatonin on the force of spontaneous contractions of in vitro rat small and large intestine. J. Pineal Res. 1986; 3: 277—284.
63. Bubenik G. A., Dhanvantari S. Influence of serotonin and melatonin on some parameters of gastrointestinal activity. J. Pineal Res. 1989; 7: 333—344.
64. Satake N., Shibata S. et al. The inhibitory action of MEL on the contractile response to 5-hydroxytryptamine in various isolated vascular smooth muscles. Gen. Pharmacol. 1986; 17: 553—558.
65. Talley N. J. Review article: 5-hydroxytryptamine agonists and antagonists in the modulation of gastrointestinal motility and sensation: clinical implications. Aliment. Pharmacol. Ther. 1992; 6: 273—289.
66. Shibata S. et al. Vasorelaxing action of melatonin in rabbit basilar artery. Gen. Pharmacol. 1989; 20: 677—680.
67. Girouard H. et al. Vasorelaxant effects of the chronic treatment with melatonin on mesenteric artery and aorta of spontaneously hypertensive rats J. Hypertens. 2001; 19: 1369—1377.
68. Konturek P. C., Konturek S. J., Majka J. et al. Melatonin affords protection against gastric lesions induced by ischemia-reperfusion possibly due to its antioxidant and mucosal microcirculatory effects. Eur. J. Pharmacol. 1997; 322. 73—77.
69. Weissbluth L., Weissbluth M. Infant colic: the effect of serotonin and melatonin circadian rhythms on the intestinal smooth muscle. Med. Hypothes. 1992; 39: 164—167.
70. Zerek-Melen G., Lewinski A., Kulak J. The opposite effect of high and low doses of melatonin on mitotic activity of the mouse intestinal epithelium. Endokrinol. Pol. 1987; 38: 317—323.
71. Wajs E., Lewinski A. Melatonin and N-acetylserotonin — two pineal indoleamines inhibiting the proliferation of the jejunal epithelial cells in the rat. Med. Sci. Res. 1988; 16: 1125—1126.
72. Strack J. M. Phenotypic plasticity, cellular-dynamics, and epithelial turnover of the intestine of Japanese-quail (Coturnix — Cotunix-Japonica). J. Zool. 1996; 238: 53—79.
73. Wetterberg L., Eberhard G. et al. The influence of age, sex, height, weight, urine volume and latitude on melatonin concentration in urine from normal subjects: a multinational study. In: Wetterberg L. eds. Light and biological rhythms in man. Oxford: Pergamon Press; 1993. 275—286.
74. Смирнов К. М., Аникина Е. К. Сезонные особенности суточного ритма у детей 3—7 лет на Крайнем Севере. В кн.: Циркадные ритмы человека и животных. Фрунзе; 1975. 259—260.
75. Horne J. A., Coyne S. Seasonal changes in the circadian variation of oral temperature during wakefulness. Experientia 1975; 31: 464—470.
76. Korhonen H., Niemela P., Tuuri H. Seasonal changes in platform use by farmed blue foxes (Alopex-Lagopus). Appl. Animal Behav. 1996; 48: 99—114.
77. Davis S., Kaune W. T. et al. Residental magnetic fields, light-at-night and nocturnal urinary 6-sulfatoxymelatonin concentration in women. Am. J. Epidemiol. 2001; 154: 591—600.
78. Schernhammer E. S., Laden F. et al. Rotating night shifts and risk of breast cancer in women participating in the nurses health study. J. Natl. Cancer Inst. 2001; 93: 1563—1568.
79. Pukkala E., Auvinen H. et al. Incidence of cancer among Finnish airline cabin attendants, 1967-92. Br. Med. J. 1995; 311: 649—652.
80. Tynes T., Hannevik M. et al. Incidence of breast cancer in Norwegian female radio and telegraph operators. Cancer Causes Control. 1996; 7: 197—204.
81. Hansen J. Increased breast cancer risk among women who work predominantly at night. Ann. Epidemiol. 2001; 12: 74—77.
82. Rafnsson V., Tulinius H. et al. Risk of breast cancer in female flight attendants: a population-based study (Iceland) Cancer Causes Control. 2001; 12: 95—101.
83. Cohen M., Lippman M., Chabner R. Role of pineal gland in aetiology and treatment of breast cancer. Lancet 1978; 2: 814—816.
84. Stevens R. G., Rea M. S. Light in the built environment: potential role of circadian disruption in endocrine disruption and breast cancer. Cancer Causes Control. 2001; 12: 279—287.
85. Fujino Y., Mizroue T., Izumi H. et al. Job stress and mental health among permanent night workers. J. Occup. Hlth 2001; 43: 301—306.
86. Anisimov V. N., Popovich I. G. et al. Melatonin and colon carcinogenesis. III. Effect of melatonin on proliferative activity and apoptosis in colon mucosa and colon tumors induced by 1,2-dimethy1hydrazine in rats. Exp. Toxicol. Pathol. 2000; 52: 71—76.
87. Blask D. E. The pineal: an oncostatic gland. In: Reiter R. J. ed. The pineal gland. New York: Raven Press; 1984. 253—284.
88. Anisimov V. N., Popovich I. G. et al. Melatonin and colon carcinogenesis: I: Inhibitory effect of melatonin on development of intestinal tumours induced by 1,2-dimethylhydrazine in rats. Carcinogenesis 1997; 18: 1549—1553.
89. Poon A. M., Mak A. S., Luk H. A. T. Melatonin and 2[125J]iodomelatonin binding sites in the human colon. Endocr. Res. 1996; 22: 77—94.
90. Bartsch C., Bartsch H. et al. Serial transplants of DMBA-indused mammary tumours in Fisher rats as a model system for human breast cancer. VI: The role of different forms of tumour-associated stress for the regulation of pineal melatonin secretion. Oncology 1999; 56: 169—176.
91. Maestroni G. J., Conti A. lmmuno-derived opioids as mediators of the immuno-enhancing and anti-stress action of melatonin. Acta Neurol. (Napoli) 1991; 13: 356—360.