Melatonin, a potential therapeutic agent for smooth muscle-related pathological conditions and aging

Current Medicinal Chemistry

Volumn 17, Issue 34, 2010, Pages 4150-4165

  Pozo, M J ^a   Gomez Pinilla, P J ^a   Camello Almaraz, C ^a   Martin Cano, F E ^a   Pascua, P ^a   Rol, M A ^b   Acuna Castroviejo D ^c   Camello, P J ^a  

^a UNIVERSITY OF EXTREMADURA   (Spain)

^b UNIVERSITY OF MURCIA   (Spain)

^c UNIVERSITY OF GRANADA   (Spain)

Author keywords

Aging; Bladder; Blood pressure; Gut; Inflammation; Melatonin; Smooth muscle

Indexed keywords

MELATONIN; MELATONIN RECEPTOR; NITRIC OXIDE;

AGING; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ARTICLE; BLADDER; BLOOD VESSEL TONE; CELL POLARITY; CHOLECYSTITIS; CONSTIPATION; DRUG MECHANISM; DRUG POTENCY; GALLBLADDER; GALLBLADDER CONTRACTION; GASTROESOPHAGEAL REFLUX; GASTROINTESTINAL TRACT; HUMAN; HYPERTENSION; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; INTESTINE TRANSIT TIME; MYOMETRIUM; NONHUMAN; OXIDATION; OXIDATIVE STRESS; SMOOTH MUSCLE; SMOOTH MUSCLE CONTRACTILITY; STOMACH;

AGING; ANIMALS; ANTIOXIDANTS; COLON; FEMALE; HUMANS; HYPERTENSION; MELATONIN; MICE; MUSCLE CONTRACTION; MUSCLE, SMOOTH; OXIDATION-REDUCTION; OXIDATIVE STRESS; PINEAL GLAND; RATS; RECEPTORS, MELATONIN; URINARY BLADDER DISEASES;

EID: 78650638685     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986710793348536     Document Type: Article

References (189)

1. Somlyo, A. P.; Somlyo, A. V. Signal transduction and regulation in smooth muscle. Nature, 1994, 372, 231-236.
2. Berridge, M. J. Inositol trisphosphate and calcium signalling. Nature, 1993, 361, 315-325.
3. Nishizuka, Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature, 1988, 334, 661-665.
4. Kamm, K. E.; Stull, J. T. The function of myosin and myosin light chain kinase phosphorylation in smooth muscle. Annu. Rev. Pharmacol. Toxicol., 1985, 25, 593-620.
5. Hori, M.; Karaki, H. Regulatory mechanisms of calcium sensitization of contractile elements in smooth muscle. Life Sci., 1998, 62, 1629-1633.
6. Somlyo, A. P.; Somlyo, A. V. Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol. Rev., 2003, 83, 1325-1358.
7. Kim, I.; Je, H. D.; Gallant, C.; Zhan, Q.; Riper, D. V.; Badwey, J. A.; Singer, H. A.; Morgan, K. G. Ca2+-calmodulin-dependent protein kinase II-dependent activation of contractility in ferret aorta. J. Physiol., 2000, 526 Pt 2, 367-374.
8. Nguyen, D. H.; Catling, A. D.; Webb, D. J.; Sankovic, M.; Walker, L. A.; Somlyo, A. V.; Weber, M. J.; Gonias, S. L. Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner. J. Cell Biol., 1999, 146, 149-164.
9. Ginnan, R.; Singer, H. A. CaM kinase II-dependent activation of tyrosine kinases and ERK1/2 in vascular smooth muscle. Am. J. Physiol Cell Physiol., 2002, 282, C754-C761.
10. Wurtman, R. J.; Axelrod, J.; Fischer, J. E. Melatonin Synthesis in the Pineal Gland: Effect of Light Mediated by the Sympathetic Nervous System. Science, 1964, 143, 1328-1329.
11. Reiter, R. J. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr. Rev., 1991, 12, 151-180.
12. Stefulj, J.; Hortner, M.; Ghosh, M.; Schauenstein, K.; Rinner, I.; Wolfler, A.; Semmler, J.; Liebmann, P. M. Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues of the rat. J. Pineal Res., 2001, 30, 243-247.
13. Kvetnoy, I. Extrapineal melatonin in pathology: new perspectives for diagnosis, prognosis and treatment of illness. Neuro. Endocrinol. Lett., 2002, 23 Suppl 1, 92-96.
14. Claustrat, B.; Brun, J.; Chazot, G. The basic physiology and pathophysiology of melatonin. Sleep Med. Rev., 2005, 9, 11-24.
15. Skene, D. J.; Papagiannidou, E.; Hashemi, E.; Snelling, J.; Lewis, D. F.; Fernandez, M.; Ioannides, C. Contribution of CYP1A2 in the hepatic metabolism of melatonin: studies with isolated microsomal preparations and liver slices. J. Pineal Res., 2001, 31, 333-342.
16. Messner, M.; Huether, G.; Lorf, T.; Ramadori, G.; Schworer, H. Presence of melatonin in the human hepatobiliary-gastrointestinal tract. Life Sci., 2001, 69, 543-551.
17. Tan, D. X.; Manchester, L. C.; Terron, M. P.; Flores, L. J.; Reiter, R. J. One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species? J. Pineal Res., 2007, 42, 28-42.
18. Ekmekcioglu, C. Melatonin receptors in humans: biological role and clinical relevance. Biomed. Pharmacother., 2006, 60, 97-108.
19. Pandi-Perumal, S. R.; Trakht, I.; Srinivasan, V.; Spence, D. W.; Maestroni, G. J.; Zisapel, N.; Cardinali, D. P. Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog. Neurobiol., 2008, 85, 335-353.
20. Witt-Enderby, P. A.; Radio, N. M.; Doctor, J. S.; Davis, V. L. Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy. J. Pineal Res., 2006, 41, 297-305.
21. Masana, M. I.; Dubocovich, M. L. Melatonin receptor signaling: finding the path through the dark. Sci. STKE., 2001, 2001, e39.
22. Steinhilber, D.; Brungs, M.; Werz, O.; Wiesenberg, I.; Danielsson, C.; Kahlen, J. P.; Nayeri, S.; Schrader, M.; Carlberg, C. The nuclear receptor for melatonin represses 5-lipoxygenase gene expression in human B lymphocytes. J. Biol. Chem., 1995, 270, 7037-7040.
23. Benitez-King, G.; Anton-Tay, F. Calmodulin mediates melatonin cytoskeletal effects. Experientia, 1993, 49, 635-641.
24. Macias, M.; Escames, G.; Leon, J.; Coto, A.; Sbihi, Y.; Osuna, A.; Acuña-Castroviejo, D. Calreticulin-melatonin. An unexpected relationship. Eur. J. Biochem., 2003, 270, 832-840.
25. Benitez-King, G. Melatonin as a cytoskeletal modulator: implications for cell physiology and disease. J. Pineal Res., 2006, 40, 1-9.
26. Sanchez-Barcelo, E. J.; Cos, S.; Mediavilla, D.; Martinez-Campa, C.; Gonzalez, A.; Alonso-Gonzalez, C. Melatonin-estrogen interactions in breast cancer. J. Pineal Res., 2005, 38, 217-222.
27. Leon, J.; Macias, M.; Escames, G.; Camacho, E.; Khaldy, H.; Martin, M.; Espinosa, A.; Gallo, M. A.; Acuña-Castroviejo, D. Structure-related inhibition of calmodulin-dependent neuronal nitricoxide synthase activity by melatonin and synthetic kynurenines. Mol. Pharmacol., 2000, 58, 967-975.
28. Tan D. X., Chen L. D., Poeggeler B., Manchester L. C., Reiter R. J. Melatonin: a potent, endogenous hydroxyl radical scavenger. 1 ed. 1993, 57.
29. Reiter, R. J.; Tan, D. X.; Terron, M. P.; Flores, L. J.; Czarnocki, Z. Melatonin and its metabolites: new findings regarding their production and their radical scavenging actions. Acta Biochim. Pol., 2007, 54, 1-9.
30. Tan, D. X.; Hardeland, R.; Manchester, L. C.; Poeggeler, B.; Lopez-Burillo, S.; Mayo, J. C.; Sainz, R. M.; Reiter, R. J. Mechanistic and comparative studies of melatonin and classic antioxidants in terms of their interactions with the ABTS cation radical. J. Pineal Res., 2003, 34, 249-259.
31. Hardeland, R.; Tan, D. X.; Reiter, R. J. Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines. J. Pineal Res., 2009, 47, 109-126.
32. de Almeida, E. A.; Martinez, G. R.; Klitzke, C. F.; de Medeiros, M. H.; Di, M. P. Oxidation of melatonin by singlet molecular oxygen (O2 (1deltag)) produces N1-acetyl-N2-formyl-5-methoxykynurenine. J. Pineal Res., 2003, 35, 131-137.
33. Zhang, H.; Squadrito, G. L.; Pryor, W. A. The reaction of melatonin with peroxynitrite: formation of melatonin radical cation and absence of stable nitrated products. Biochem. Biophys. Res. Commun., 1998, 251, 83-87.
34. Tan, D. X.; Manchester, L. C.; Burkhardt, S.; Sainz, R. M.; Mayo, J. C.; Kohen, R.; Shohami, E.; Huo, Y. S.; Hardeland, R.; Reiter, R. J. N1-acetyl-N2-formyl-5-methoxykynuramine, a biogenic amine and melatonin metabolite, functions as a potent antioxidant. FASEB J., 2001, 15, 2294-2296.
35. Guenther, A. L.; Schmidt, S. I.; Laatsch, H.; Fotso, S.; Ness, H.; Ressmeyer, A. R.; Poeggeler, B.; Hardeland, R. Reactions of the melatonin metabolite AMK (N1-acetyl-5-methoxykynuramine) with reactive nitrogen species: formation of novel compounds, 3-acetamidomethyl-6-methoxycinnolinone and 3-nitro-AMK. J. Pineal Res., 2005, 39, 251-260.
36. Figueroa, J. P.; Honnebier, M. B.; Jenkins, S.; Nathanielsz, P. W. Alteration of 24-hour rhythms in myometrial activity in the chronically catheterized pregnant rhesus monkey after a 6-hour shift in the light-dark cycle. Am. J. Obstet. Gynecol., 1990, 163, 648-654.
37. Andreadou, I.; Tsantili-Kakoulidou, A.; Spyropoulou, E.; Siatra, T. Reactions of indole derivatives with cardioprotective activity with reactive oxygen species. Comparison with melatonin. Chem. Pharm. Bull. (Tokyo), 2003, 51, 1128-1131.
38. Rodriguez, C.; Mayo, J. C.; Sainz, R. M.; Antolin, I.; Herrera, F.; Martin, V.; Reiter, R. J. Regulation of antioxidant enzymes: a significant role for melatonin. J. Pineal Res., 2004, 36, 1-9.
39. Dziegiel, P.; Murawska-Cialowicz, E.; Jethon, Z.; Januszewska, L.; Podhorska-Okolow, M.; Surowiak, P.; Zawadzki, M.; Rabczynski, J.; Zabel, M. Melatonin stimulates the activity of protective antioxidative enzymes in myocardial cells of rats in the course of doxorubicin intoxication. J. Pineal Res., 2003, 35, 183-187.
40. Crespo, E.; Macias, M.; Pozo, D.; Escames, G.; Martin, M.; Vives, F.; Guerrero, J. M.; Acuña-Castroviejo, D. Melatonin inhibits expression of the inducible NO synthase II in liver and lung and prevents endotoxemia in lipopolysaccharide-induced multiple organ dysfunction syndrome in rats. FASEBJ., 1999, 13, 1537-1546.
41. Gomez-Pinilla, P. J.; Camello, P. J.; Pozo, M. J. Protective effect of melatonin on Ca2+ homeostasis and contractility in acute cholecystitis. J. Pineal Res., 2008, 44, 250-260.
42. Gomez-Pinilla, P. J.; Camello, P. J.; Pozo, M. J. Effects of melatonin on gallbladder neuromuscular function in acute cholecystitis. J. Pharmacol. Exp. Ther., 2007, 323, 138-146.
43. Gomez-Pinilla, P. J.; Pozo, M. J.; Camello, P. J. Aging impairs neurogenic contraction in guinea pig urinary bladder: role of oxidative stress and melatonin. Am. J. Physiol Regul. Integr. Comp. Physiol., 2007, 293, R793-R803.
44. Allegra, M.; Reiter, R. J.; Tan, D. X.; Gentile, C.; Tesoriere, L.; Livrea, M. A. The chemistry of melatonin's interaction with reactive species. J. Pineal Res., 2003, 34, 1-10.
45. Tan, D. X.; Manchester, L. C.; Hardeland, R.; Lopez-Burillo, S.; Mayo, J. C.; Sainz, R. M.; Reiter, R. J. Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. J. Pineal Res., 2003, 34, 75-78.
46. Reiter, R. J.; Tan, D. X.; Gitto, E.; Sainz, R. M.; Mayo, J. C.; Leon, J.; Manchester, L. C.; Vijaya Laxmi; Kilic, E.; Kilic, U. Pharmacological utility of melatonin in reducing oxidative cellular and molecular damage. Pol. J. Pharmacol., 2004, 56, 159-170.
47. Acuña, C. D.; Escames, G.; Carazo, A.; Leon, J.; Khaldy, H.; Reiter, R. J. Melatonin, mitochondrial homeostasis and mitochondrialrelated diseases. Curr. Top. Med. Chem., 2002, 2, 133-151.
48. Grant, S. G.; Melan, M. A.; Latimer, J. J.; Witt-Enderby, P. A. Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives. Expert Rev. Mol. Med., 2009, 11, e5.
49. Jahnke, G.; Marr, M.; Myers, C.; Wilson, R.; Travlos, G.; Price, C. Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats. Toxicol. Sci., 1999, 50, 271-279.
50. Nordlund, J. J.; Lerner, A. B. The effects of oral melatonin on skin color and on the release of pituitary hormones. J. Clin. Endocrinol. Metab., 1977, 45, 768-774.
51. Luboshitzky, R.; Levi, M.; Shen-Orr, Z.; Blumenfeld, Z.; Herer, P.; Lavie, P. Long-term melatonin administration does not alter pituitary-gonadal hormone secretion in normal men. Hum. Reprod., 2000, 15, 60-65.
52. Molina-Carballo, A.; Munoz-Hoyos, A.; Reiter, R. J.; Sanchez-Forte, M.; Moreno-Madrid, F.; Rufo-Campos, M.; Molina-Font, J. A.; Acuña-Castroviejo, D. Utility of high doses of melatonin as adjunctive anticonvulsant therapy in a child with severe myoclonic epilepsy: two years' experience. J. Pineal Res., 1997, 23, 97-105.
53. Chahbouni, M.; Escames, G.; Venegas, C.; Sevilla, B.; Garcia, J. A.; Lopez, L. C.; Munoz-Hoyos, A.; Molina-Carballo, A.; Acuña-Castroviejo, D. Melatonin treatment normalizes plasma proinflammatory cytokines and nitrosative/oxidative stress in patients suffering from Duchenne muscular dystrophy. J. Pineal Res., 2010, 48, 282-289.
54. Williamson, B. L.; Tomlinson, A. J.; Naylor, S.; Gleich, G. J. Contaminants in commercial preparations of melatonin. Mayo Clin. Proc., 1997, 72, 1094-1095.
55. Hermida, R. C.; Ayala, D. E.; Fernandez, J. R.; Mojon, A.; Alonso, I.; Calvo, C. Modeling the circadian variability of ambulatorily monitored blood pressure by multiple-component analysis. Chronobiol. Int., 2002, 19, 461-481.
56. Booth, A. O.; Nowson, C. A. Patient recall of receiving lifestyle advice for overweight and hypertension from their General Practitioner. BMC. Fam. Pract., 2010, 11, 8.
57. Pinto, E. Blood pressure and ageing. Postgrad. Med. J., 2007, 83, 109-114.
58. Sewerynek, E. Melatonin and the cardiovascular system. Neuro. Endocrinol. Lett., 2002, 23 Suppl 1, 79-83.
59. Greenwald, S. E. Ageing of the conduit arteries. J. Pathol., 2007, 211, 157-172.
60. Mattson, M. P.; Kruman, I. I.; Duan, W. Folic acid and homocysteine in age-related disease. Ageing Res. Rev., 2002, 1, 95-111.
61. Moncada, S.; Higgs, E. A. The discovery of nitric oxide and its role in vascular biology. Br. J. Pharmacol., 2006, 147 Suppl 1, S193-S201.
62. Dupuis, F.; Regrigny, O.; Atkinson, J.; Liminana, P.; Delagrange, P.; Scalbert, E.; Chillon, J. M. Impact of treatment with melatonin on cerebral circulation in old rats. Br. J. Pharmacol., 2004, 141, 399-406.
63. Murawska-Cialowicz, E.; Januszewska, L.; Zuwala-Jagiello, J.; Milczarska, J.; Zawadzki, M.; Paprocka-Borowicz, M.; Wierzbicka-Damska, I. Melatonin decreases homocysteine level in blood of rats. J. Physiol. Pharmacol., 2008, 59, 717-729.
64. Vanecek, J. Cellular mechanisms of melatonin action. Physiol. Rev., 1998, 78, 687-721.
65. Zanoboni, A.; Forni, A.; Zanoboni-Muciaccia, W.; Zanussi, C. Effect of pinealectomy on arterial blood pressure and food and water intake in the rat. J. Endocrinol. Invest, 1978, 1, 125-130.
66. Cunnane, S. C.; Manku, M. S.; Oka, M.; Horrobin, D. F. Enhanced vascular reactivity to various vasoconstrictor agents following pinealectomy in the rat: role of melatonin. Can. J. Physiol. Pharmacol., 1980, 58, 287-293.
67. Kurcer, Z.; Sahna, E.; Olmez, E. Vascular reactivity to various vasoconstrictor agents and endothelium-dependent relaxations of rat thoracic aorta in the long-term period of pinealectomy. J. Pharmacol. Sci., 2006, 101, 329-334.
68. Cagnacci, A.; Arangino, S.; Angiolucci, M.; Maschio, E.; Melis, G. B. Influences of melatonin administration on the circulation of women. Am. J. Physiol, 1998, 274, R335-R338.
69. Arangino, S.; Cagnacci, A.; Angiolucci, M.; Vacca, A. M.; Longu, G.; Volpe, A.; Melis, G. B. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am. J. Cardiol., 1999, 83, 1417-1419.
70. Yildiz, M.; Akdemir, O. Assessment of the effects of physiological release of melatonin on arterial distensibility and blood pressure. Cardiol. Young, 2009, 19, 198-203.
71. Tranquilli, A. L.; Turi, A.; Giannubilo, S. R.; Garbati, E. Circadian melatonin concentration rhythm is lost in pregnant women with altered blood pressure rhythm. Gynecol. Endocrinol., 2004, 18, 124-129.
72. Zeman, M.; Dulkova, K.; Bada, V.; Herichova, I. Plasma melatonin concentrations in hypertensive patients with the dipping and nondipping blood pressure profile. Life Sci., 2005, 76, 1795-1803.
73. Grossman, E.; Laudon, M.; Yalcin, R.; Zengil, H.; Peleg, E.; Sharabi, Y.; Kamari, Y.; Shen-Orr, Z.; Zisapel, N. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am. J. Med., 2006, 119, 898-902.
74. Cagnacci, A.; Cannoletta, M.; Renzi, A.; Baldassari, F.; Arangino, S.; Volpe, A. Prolonged melatonin administration decreases nocturnal blood pressure in women. Am. J. Hypertens., 2005, 18, 1614-1618.
75. Cavallo, A.; Daniels, S. R.; Dolan, L. M.; Bean, J. A.; Khoury, J. C. Blood pressure-lowering effect of melatonin in type 1 diabetes. J. Pineal Res., 2004, 36, 262-266.
76. Androulakis, E. S.; Tousoulis, D.; Papageorgiou, N.; Tsioufis, C.; Kallikazaros, I.; Stefanadis, C. Essential hypertension: is there a role for inflammatory mechanisms? Cardiol. Rev., 2009, 17, 216-221.
77. Aktan, F. iNOS-mediated nitric oxide production and its regulation. Life Sci., 2004, 75, 639-653.
78. Forstermann, U. Oxidative stress in vascular disease: causes, defense mechanisms and potential therapies. Nat. Clin. Pract. Cardiovasc. Med., 2008, 5, 338-349.
79. Reyes-Toso, C. F.; Linares, L. M.; Albornoz, L. E.; Obaya-Naredo, D.; Wallinger, M. L.; Ricci, C. R.; Cardinali, D. P. Comparative effects of melatonin and vitamin e in restoring aortic relaxation in pancreatectomized rats. J. Physiol Biochem., 2006, 62, 207-212.
80. Muller-Schweinitzer, E.; Gilles, H.; Grapow, M.; Kern, T.; Reineke, D.; Zerkowski, H. R. Attenuation of lipopolysaccharideinduced hyperreactivity of human internal mammary arteries by melatonin. J. Pineal Res., 2004, 37, 92-97.
81. Zhou, J. L.; Zhu, X. G.; Ling, Y. L.; Li, Q. Melatonin reduces peroxynitrite-induced injury in aortic smooth muscle cells. Acta Pharmacol. Sin., 2004, 25, 186-190.
82. Okatani, Y.; Wakatsuki, A.; Reiter, R. J. Melatonin suppresses homocysteine enhancement of serotonin-induced vasoconstriction in the human umbilical artery. J. Pineal Res., 2001, 31, 242-247.
83. Wu, L.; Wang, R.; de, C. J. Enhanced inhibition by melatonin of alpha-adrenoceptor-induced aortic contraction and inositol phosphate production in vascular smooth muscle cells from spontaneously hypertensive rats. J. Hypertens., 1998, 16, 339-347.
84. Rodella, L. F.; Filippini, F.; Bonomini, F.; Bresciani, R.; Reiter, R. J.; Rezzani, R. Beneficial effects of melatonin on nicotineinduced vasculopathy. J. Pineal Res., 2010, 48, 126-132.
85. Pechanova, O.; Simko, F. Chronic antioxidant therapy fails to ameliorate hypertension: potential mechanisms behind. J. Hypertens., 2009, 27 Suppl 6, S32-S36.
86. Escames, G.; Khaldy, H.; Leon, J.; Gonzalez, L.; Acuña-Castroviejo, D. Changes in iNOS activity, oxidative stress and melatonin levels in hypertensive patients treated with lacidipine. J. Hypertens., 2004, 22, 629-635.
87. Addabbo, F.; Montagnani, M.; Goligorsky, M. S. Mitochondria and reactive oxygen species. Hypertension, 2009, 53, 885-892.
88. Thomas, S. R.; Witting, P. K.; Drummond, G. R. Redox control of endothelial function and dysfunction: molecular mechanisms and therapeutic opportunities. Antioxid. Redox. Signal., 2008, 10, 1713-1765.
89. Zimmerman, M. C.; Zucker, I. H. Mitochondrial dysfunction and mitochondrial-produced reactive oxygen species: new targets for neurogenic hypertension? Hypertension, 2009, 53, 112-114.
90. Chan, S. H.; Wu, K. L.; Chang, A. Y.; Tai, M. H.; Chan, J. Y. Oxidative impairment of mitochondrial electron transport chain complexes in rostral ventrolateral medulla contributes to neurogenic hypertension. Hypertension, 2009, 53, 217-227.
91. Doughan, A. K.; Harrison, D. G.; Dikalov, S. I. Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circ. Res., 2008, 102, 488-496.
92. Escames, G.; Leon, J.; Macias, M.; Khaldy, H.; Acuña-Castroviejo, D. Melatonin counteracts lipopolysaccharide-induced expression and activity of mitochondrial nitric oxide synthase in rats. FA S e B J., 2003, 17, 932-934.
93. Giacomo, C. G.; Antonio, M. Melatonin in cardiac ischemia/reperfusion- induced mitochondrial adaptive changes. Cardiovasc. Hematol. Disord. Drug Targets, 2007, 7, 163-169.
94. Rodriguez, M. I.; Carretero, M.; Escames, G.; Lopez, L. C.; Maldonado, M. D.; Tan, D. X.; Reiter, R. J.; Acuña-Castroviejo, D. Chronic melatonin treatment prevents age-dependent cardiac mitochondrial dysfunction in senescence-accelerated mice. Free Radic. Res., 2007, 41, 15-24.
95. Viswanathan, M.; Laitinen, J. T.; Saavedra, J. M. Expression of melatonin receptors in arteries involved in thermoregulation. Proc. Natl. Acad. Sci. U. S. A, 1990, 87, 6200-6203.
96. Seltzer, A.; Viswanathan, M.; Saavedra, J. M. Melatonin-binding sites in brain and caudal arteries of the female rat during the estrous cycle and after estrogen administration. Endocrinology, 1992, 130, 1896-1902.
97. Capsoni, S.; Viswanathan, M.; De Oliveira, A. M.; Saavedra, J. M. Characterization of melatonin receptors and signal transduction system in rat arteries forming the circle of Willis. Endocrinology, 1994, 135, 373-378.
98. Masana, M. I.; Doolen, S.; Ersahin, C.; Al-Ghoul, W. M.; Duckles, S. P.; Dubocovich, M. L.; Krause, D. N. MT (2) melatonin receptors are present and functional in rat caudal artery. J. Pharmacol. Exp. Ther., 2002, 302, 1295-1302.
99. Cui, P.; Yu, M.; Luo, Z.; Dai, M.; Han, J.; Xiu, R.; Yang, Z. Intracellular signaling pathways involved in cell growth inhibition of human umbilical vein endothelial cells by melatonin. J. Pineal Res., 2008, 44, 107-114.
100. Silva, C. L.; Tamura, E. K.; Macedo, S. M.; Cecon, E.; Bueno-Alves, L.; Farsky, S. H.; Ferreira, Z. S.; Markus, R. P. Melatonin inhibits nitric oxide production by microvascular endothelial cells in vivo and in vitro. Br. J. Pharmacol., 2007, 151, 195-205.
101. von, G. C.; Stehle, J. H.; Weaver, D. R. Mammalian melatonin receptors: molecular biology and signal transduction. Cell Tissue Res., 2002, 309, 151-162.
102. Lew, M. J.; Flanders, S. Mechanisms of melatonin-induced vasoconstriction in the rat tail artery: a paradigm of weak vasoconstriction. B r. J. Pharmacol., 1999, 126, 1408-1418.
103. Ting, K. N.; Blaylock, N. A.; Sugden, D.; Delagrange, P.; Scalbert, E.; Wilson, V. G. Molecular and pharmacological evidence for MT1 melatonin receptor subtype in the tail artery of juvenile Wistar rats. Br. J. Pharmacol., 1999, 127, 987-995.
104. Geary, G. G.; Duckles, S. P.; Krause, D. N. Effect of melatonin in the rat tail artery: role of K+ channels and endothelial factors. Br. J. Pharmacol., 1998, 123, 1533-1540.
105. Girouard, H.; de, C. J. Inhibitory effect of melatonin on alpha1-adrenergic-induced vasoconstriction in mesenteric beds of spontaneously hypertensive rats. Am. J. Hypertens., 2004, 17, 339-346.
106. Pogan, L.; Bissonnette, P.; Parent, L.; Sauve, R. The effects of melatonin on Ca (2+) homeostasis in endothelial cells. J. Pineal Res., 2002, 33, 37-47.
107. Thiemermann, C. Nitric oxide and septic shock. Gen. Pharmacol., 1997, 29, 159-166.
108. Tamura, E. K.; Cecon, E.; Monteiro, A. W.; Silva, C. L.; Markus, R. P. Melatonin inhibits LPS-induced NO production in rat endothelial cells. J. Pineal Res., 2009, 46, 268-274.
109. Escames, G.; Acuña-Castroviejo, D.; Lopez, L. C.; Tan, D. X.; Maldonado, M. D.; Sanchez-Hidalgo, M.; Leon, J.; Reiter, R. J. Pharmacological utility of melatonin in the treatment of septic shock: experimental and clinical evidence. J. Pharm. Pharmacol., 2006, 58, 1153-1165.
110. Rodriguez, M. I.; Escames, G.; Lopez, L. C.; Garcia, J. A.; Ortiz, F.; Lopez, A.; Acuña-Castroviejo, D. Melatonin administration prevents cardiac and diaphragmatic mitochondrial oxidative damage in senescence-accelerated mice. J. Endocrinol., 2007, 194, 637-643.
111. Ferrario, C. M.; Barnes, K. L.; Szilagyi, J. E.; Brosnihan, K. B. Physiological and pharmacological characterization of the area postrema pressor pathways in the normal dog. Hypertension, 1979, 1, 235-245.
112. Price, C. J.; Hoyda, T. D.; Ferguson, A. V. The area postrema: a brain monitor and integrator of systemic autonomic state. Neuroscientist., 2008, 14, 182-194.
113. Osborn, J. W.; Jacob, F.; Guzman, P. A neural set point for the long-term control of arterial pressure: beyond the arterial baroreceptor reflex. Am. J. Physiol Regul. Integr. Comp Physiol, 2005, 288, R846-R855.
114. Ferguson, A. V. The area postrema: a cardiovascular control centre at the blood-brain interface? Can. J. Physiol Pharmacol., 1991, 69, 1026-1034.
115. Williams, L. M.; Hannah, L. T.; Hastings, M. H.; Maywood, E. S. Melatonin receptors in the rat brain and pituitary. J. Pineal Res., 1995, 19, 173-177.
116. Viswanathan, M.; Laitinen, J. T.; Saavedra, J. M. Differential expression of melatonin receptors in spontaneously hypertensive rats. Neuroendocrinology, 1992, 56, 864-870.
117. Irmak, M. K.; Sizlan, A. Essential hypertension seems to result from melatonin-induced epigenetic modifications in area postrema. Med. Hypotheses, 2006, 66, 1000-1007.
118. Laflamme, A.; Wu, L.; Foucart, S.; de, C. J. Impaired basal sympathetic tone and alpha1-adrenergic responsiveness in association with the hypotensive effect of melatonin in spontaneously hypertensive rats. Am. J. Hypertens., 1998, 11, 219-229.
119. Nishiyama, K.; Yasue, H.; Moriyama, Y.; Tsunoda, R.; Ogawa, H.; Yoshimura, M.; Kugiyama, K. Acute effects of melatonin administration on cardiovascular autonomic regulation in healthy men. Am. Heart J., 2001, 141, E9.
120. Raikhlin, N. T.; Kvetnoy, I. M.; Tolkachev, V. N. Melatonin may be synthesised in enterochromaffin cells. Nature, 1975, 255, 344-345.
121. Bubenik, G. A.; Brown, G. M. Pinealectomy reduces melatonin levels in the serum but not in the gastrointestinal tract of rats. Biol. Signals, 1997, 6, 40-44.
122. Bubenik, G. A. Thirty four years since the discovery of gastrointestinal melatonin. J. Physiol Pharmacol., 2008, 59 Suppl 2, 33-51.
123. Sjoblom, M.; Flemstrom, G. Melatonin in the duodenal lumen is a potent stimulant of mucosal bicarbonate secretion. J. Pineal Res., 2003, 34, 288-293.
124. Jaworek, J.; Brzozowski, T.; Konturek, S. J. Melatonin as an organoprotector in the stomach and the pancreas. J. Pineal Res., 2005, 38, 73-83.
125. Jaworek, J. Ghrelin and melatonin in the regulation of pancreatic exocrine secretion and maintaining of integrity. J. Physiol Pharmacol., 2006, 57 Suppl 5, 83-96.
126. Drago, F.; Macauda, S.; Salehi, S. Small doses of melatonin increase intestinal motility in rats. Dig. Dis. Sci., 2002, 47, 1969-1974.
127. Reyes-Vazquez, C.; Naranjo-Rodriguez, E. B.; Garcia-Segoviano, J. A.; Trujillo-Santana, J. T.; Prieto-Gomez, B. Apamin blocks the direct relaxant effect of melatonin on rat ileal smooth muscle. J. Pineal Res., 1997, 22, 1-8.
128. Harlow, H. J.; Weekley, 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.
129. Bubenik, G. A. The effect of serotonin, N-acetylserotonin, and melatonin on spontaneous contractions of isolated rat intestine. J. Pineal Res., 1986, 3, 41-54.
130. Bertrand, P. P.; Bertrand, R. L.; Camello, P. J.; Pozo, M. J. Simultaneous measurement of serotonin and melatonin from the intestine of old mice: the effects of daily melatonin supplementation. J. Pineal Res., 2010, 49, 23-34.
131. Stebelova, K.; Anttila, K.; Manttari, S.; Saarela, S.; Zeman, M. Immunohistochemical definition of MT (2) receptors and melatonin in the gastrointestinal tissues of rat. Acta Histochem., 2010, 112, 26-33.
132. Storr, M.; Koppitz, P.; Sibaev, A.; Saur, D.; Kurjak, M.; Franck, H.; Schusdziarra, V.; Allescher, H. D. Melatonin reduces nonadrenergic, non-cholinergic relaxant neurotransmission by inhibition of nitric oxide synthase activity in the gastrointestinal tract of rodents in vitro. J. Pineal Res., 2002, 33, 101-108.
133. de Souza, P. R. Regression of an esophageal ulcer using a dietary supplement containing melatonin. J. Pineal Res., 2006, 40, 355-356.
134. de Souza, P. R. Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole. J. Pineal Res., 2006, 41, 195-200.
135. Klupinska, G.; Wisniewska-Jarosinska, M.; Harasiuk, A.; Chojnacki, C.; Stec-Michalska, K.; Blasiak, J.; Reiter, R. J.; Chojnacki, J. Nocturnal secretion of melatonin in patients with upper digestive tract disorders. J. Physiol Pharmacol., 2006, 57 Suppl 5, 41-50.
136. Konturek, S. J.; Zayachkivska, O.; Havryluk, X. O.; Brzozowski, T.; Sliwowski, Z.; Pawlik, M.; Konturek, P. C.; Czesnikiewicz-Guzik, M.; Gzhegotsky, M. R.; Pawlik, W. W. Protective influence of melatonin against acute esophageal lesions involves prostaglandins, nitric oxide and sensory nerves. J. Physiol Pharmacol., 2007, 58, 361-377.
137. Martin, M. T.; Azpiroz, F.; Malagelada, J. R. Melatonin and the gastrointestinal tract. Therapie, 1998, 53, 453-458.
138. Kasimay, O.; Cakir, B.; Devseren, E.; Yegen, B. C. Exogenous melatonin delays gastric emptying rate in rats: role of CCK2 and 5-HT3 receptors. J. Physiol. Pharmacol., 2005, 56, 543-553.
139. Konturek, S. J.; Konturek, P. C.; Brzozowski, T.; Bubenik, G. A. Role of melatonin in upper gastrointestinal tract. J. Physiol Pharmacol., 2007, 58 Suppl 6, 23-52.
140. Konturek, P. C.; Konturek, S. J.; Brzozowski, T.; Dembinski, A.; Zembala, M.; Mytar, B.; Hahn, E. G. Gastroprotective activity of melatonin and its precursor, L-tryptophan, against stress-induced and ischaemia-induced lesions is mediated by scavenge of oxygen radicals. Scand. J. Gastroenterol., 1997, 32, 433-438.
141. Brzozowska, I.; Konturek, P. C.; Brzozowski, T.; Konturek, S. J.; Kwiecien, S.; Pajdo, R.; Drozdowicz, D.; Pawlik, M.; Ptak, A.; Hahn, E. G. Role of prostaglandins, nitric oxide, sensory nerves and gastrin in acceleration of ulcer healing by melatonin and its precursor, L-tryptophan. J. Pineal Res., 2002, 32, 149-162.
142. Tan, D.; Manchester, L. C.; Reiter, R. J.; Qi, W.; Hanes, M. A.; Farley, N. J. High physiological levels of melatonin in the bile of mammals. Life Sci., 1999, 65, 2523-2529.
143. Koppisetti, S.; Jenigiri, B.; Terron, M. P.; Tengattini, S.; Tamura, H.; Flores, L. J.; Tan, D. X.; Reiter, R. J. Reactive oxygen species and the hypomotility of the gall bladder as targets for the treatment of gallstones with melatonin: a review. Dig. Dis. Sci., 2008, 53, 2592-2603.
144. Hussain, S. A. Effect of melatonin on cholesterol absorption in rats. J. Pineal Res., 2007, 42, 267-271.
145. Gomez-Pinilla, P. J.; Camello-Almaraz, C.; Moreno, R.; Camello, P. J.; Pozo, M. J. Melatonin treatment reverts age-related changes in Guinea pig gallbladder neuromuscular transmission and contractility. J. Pharmacol. Exp. Ther., 2006, 319, 847-856.
146. Morales, S.; Camello, P. J.; Alcon, S.; Salido, G. M.; Mawe, G.; Pozo, M. J. Coactivation of capacitative calcium entry and L-type calcium channels in guinea pig gallbladder. Am. J. Physiol. Gastrointest. Liver Physiol., 2004, 286, G1090-G1100.
147. Gomez-Pinilla, P. J.; Morales, S.; Camello-Almaraz, C.; Moreno, R.; Pozo, M. J.; Camello, P. J. Changes in guinea pig gallbladder smooth muscle Ca2+ homeostasis by acute acalculous cholecystitis. Am. J. Physiol. Gastrointest. Liver Physiol., 2006, 290, G14-G22.
148. Mayo, J. C.; Sainz, R. M.; Tan, D. X.; Hardeland, R.; Leon, J.; Rodriguez, C.; Reiter, R. J. Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages. J. Neuroimmunol., 2005, 165, 139-149.
149. Thor, P. J.; Krolczyk, G.; Gil, K.; Zurowski, D.; Nowak, L. Melatonin and serotonin effects on gastrointestinal motility. J. Physiol Pharmacol., 2007, 58 Suppl 6, 97-103.
150. Ozacmak, V. H.; Sayan, H.; Arslan, S. O.; Altaner, S.; Aktas, R. G. Protective effect of melatonin on contractile activity and oxidative injury induced by ischemia and reperfusion of rat ileum. Life Sci., 2005, 76, 1575-1588.
151. Marquez, E.; Sanchez-Fidalgo, S.; Calvo, J. R.; la de, L. C.; Motilva, V. Acutely administered melatonin is beneficial while chronic melatonin treatment aggravates the evolution of TNBS-induced colitis. J. Pineal Res., 2006, 40, 48-55.
152. Mei, Q.; Xu, J. M.; Xiang, L.; Hu, Y. M.; Hu, X. P.; Xu, Z. W. Change of nitric oxide in experimental colitis and its inhibition by melatonin in vivo and in vitro. Postgrad. Med. J., 2005, 81, 667-672.
153. Terry, P. D.; Villinger, F.; Bubenik, G. A.; Sitaraman, S. V. Melatonin and ulcerative colitis: evidence, biological mechanisms, and future research. Inflamm. Bowel. Dis., 2009, 15, 134-140.
154. Mann, S. Melatonin for ulcerative colitis? Am. J. Gastroenterol., 2003, 98, 232-233.
155. Malhotra, S.; Bhasin, D.; Shafiq, N.; Pandhi, P. Drug treatment of ulcerative colitis: unfractionated heparin, low molecular weight heparins and beyond. Expert. Opin. Pharmacother., 2004, 5, 329-334.
156. Jan, J. E.; O'Donnell, M. E. Use of melatonin in the treatment of paediatric sleep disorders. J. Pineal Res., 1996, 21, 193-199.
157. Jan, J. E.; Freeman, R. D. Re: Mann-melatonin for ulcerative colitis? Am. J. Gastroenterol., 2003, 98, 1446.
158. Lu, W. Z.; Gwee, K. A.; Moochhalla, S.; Ho, K. Y. Melatonin improves bowel symptoms in female patients with irritable bowel syndrome: a double-blind placebo-controlled study. Aliment. Pharmacol. Ther., 2005, 22, 927-934.
159. Saha, L.; Malhotra, S.; Rana, S.; Bhasin, D.; Pandhi, P. A preliminary study of melatonin in irritable bowel syndrome. J. Clin. Gastroenterol., 2007, 41, 29-32.
160. Song, G. H.; Leng, P. H.; Gwee, K. A.; Moochhala, S. M.; Ho, K. Y. Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study. Gut, 2005, 54, 1402-1407.
161. Sener, G.; Sehirli, A. O.; Paskaloglu, K.; Dulger, G. A.; Alican, I. Melatonin treatment protects against ischemia/reperfusion-induced functional and biochemical changes in rat urinary bladder. J. Pineal Res., 2003, 34, 226-230.
162. Paskaloglu, K.; Sener, G.; Kapucu, C.; yanoglu-Dulger, G. Melatonin treatment protects against sepsis-induced functional and biochemical changes in
163. Sener, G.; Kapucu, C.; Paskaloglu, K.; Ayanoglu-Dülger, G.; Arbak, S.; Ersoy, Y.; Alican, I. Melatonin reverses urinary system and aorta damage in the rat due to chronic nicotine administration. J. Pharm. Pharmacol., 2004, 56, 359-366.
164. Cetinel, S.; Ercan, F.; Sirvanci, S.; Sehirli, O.; Ersoy, Y.; San, T.; Sener, G. The ameliorating effect of melatonin on protamine sulfate induced bladder injury and its relationship to interstitial cystitis. J. Urol., 2003, 169, 1564-1568.
165. Sadir, S.; Deveci, S.; Korkmaz, A.; Oter, S. Alpha-tocopherol, beta-carotene and melatonin administration protects cyclophosphamide-induced oxidative damage to bladder tissue in rats. Cell Biochem. Funct., 2007, 25, 521-526.
166. Topal, T.; Oztas, Y.; Korkmaz, A.; Sadir, S.; Oter, S.; Coskun, O.; Bilgic, H. Melatonin ameliorates bladder damage induced by cyclophosphamide in rats. J. Pineal Res., 2005, 38, 272-277.
167. Yildirim, I.; Korkmaz, A.; Oter, S.; Ozcan, A.; Oztas, E. Contribution of antioxidants to preventive effect of mesna in cyclophosphamide-induced hemorrhagic cystitis in rats. Cancer Chemother. Pharmacol., 2004, 54, 469-473.
168. Sener, G.; Atasoy, B. M.; Ersoy, Y.; Arbak, S.; Sengoz, M.; Yegen, B. C. Melatonin protects against ionizing radiation-induced oxidative damage in corpus cavernosum and urinary bladder in rats. J. Pineal Res., 2004, 37, 241-246.
169. Cetinel, S.; Ercan, F.; Cikler, E.; Contuk, G.; Sener, G. Protective effect of melatonin on water avoidance stress induced degeneration of the bladder. J. Urol., 2005, 173, 267-270.
170. Onur, R.; Tasdemir, C.; Seckin, D.; Ilhan, N.; Kutlu, S.; Akpolat, N. Combined use of melatonin and terazosin restores bladder contractility in rabbits with partial outlet obstruction. Urology, 2008, 72, 439-443.
171. Gomez-Pinilla, P. J.; Gomez, M. F.; Hedlund, P.; Sward, K.; Hellstrand, P.; Camello, P. J.; Pozo, M. J.; Andersson, K. E. Effect of melatonin on age associated changes in Guinea pig bladder function. J. Urol., 2007, 177, 1558-1561.
172. Hald, T.; Horn, T. The human urinary bladder in ageing. Br. J. Urol., 1998, 82 Suppl 1, 59-64.
173. Gomez-Pinilla, P. J.; Gomez, M. F.; Sward, K.; Hedlund, P.; Hellstrand, P.; Camello, P. J.; Andersson, K. E.; Pozo, M. J. Melatonin restores impaired contractility in aged guinea pig urinary bladder. J. Pineal Res., 2008, 44, 416-425.
174. Gomez-Pinilla, P. J.; Pozo, M. J.; Baba, A.; Matsuda, T.; Camello, P. J. Ca2+ extrusion in aged smooth muscle cells. Biochem. Pharmacol., 2007, 74, 860-869.
175. Onur, R.; Ozcan, M.; Tuygun, U.; Ozan, T.; Ayar, A.; Orhan, I. Effects of Combined use of Trospium Chloride and Melatonin on In vitro Contractility of Rat Urinary Bladder. Urology, 2010, 75, 873-877.
176. Semercioz, A.; Onur, R.; Ayar, A.; Orhan, I. The inhibitory role of melatonin on isolated guinea-pig urinary bladder: an endogenous hormone effect. BJU Int., 2004, 94, 1373-1376.
177. Drake, M. J.; Mills, I. W.; Noble, J. G. Melatonin pharmacotherapy for nocturia in men with benign prostatic enlargement. J. Urol., 2004, 171, 1199-1202.
178. Ducsay, C. A.; Yellon, S. M. Photoperiod regulation of uterine activity and melatonin rhythms in the pregnant rhesus macaque. Biol. Reprod., 1991, 44, 967-974.
179. Bosc, M. J. Time of parturition in rats after melatonin administration or change of photoperiod. J. Reprod. Fertil., 1987, 80, 563-568.
180. Panduro-Baron, G.; Gonzalez-Moreno, J.; Hernandez-Figueroa, E. The biorhythm of birth. Int. J. Gynaecol. Obstet., 1994, 45, 283-284.
181. Sharkey, J. T.; Puttaramu, R.; Word, R. A.; Olcese, J. Melatonin synergizes with oxytocin to enhance contractility of human myometrial smooth muscle cells. J. Clin. Endocrinol. Metab, 2009, 94, 421-427.
182. Martensson, L. G.; Andersson, R. G.; Berg, G. Melatonin together with noradrenaline augments contractions of human myometrium. Eur. J. Pharmacol., 1996, 316, 273-275.
183. Ayar, A.; Kutlu, S.; Yilmaz, B.; Kelestimur, H. Melatonin inhibits spontaneous and oxytocin-induced contractions of rat myometrium in vitro. Neuro. Endocrinol. Lett., 2001, 22, 199-207.
184. Drogovoz, S. M.; Ryzhenko, I. M. [The tocolytic activity of melatonin]. Eksp. Klin. Farmakol., 1993, 56, 23-25.
185. Abd-Allah, A. R.; El-Sayedel, S. M.; Abdel-Wahab, M. H.; Hamada, F. M. Effect of melatonin on estrogen and progesterone receptors in relation to uterine contraction in rats. Pharmacol. Res., 2003, 47, 349-354.
186. Steffens, F.; Zhou, X. B.; Sausbier, U.; Sailer, C.; Motejlek, K.; Ruth, P.; Olcese, J.; Korth, M.; Wieland, T. Melatonin receptor signaling in pregnant and nonpregnant rat uterine myocytes as probed by large conductance Ca2+-activated K+ channel activity. Mol. Endocrinol., 2003, 17, 2103-2115.
187. Schlabritz-Loutsevitch, N.; Hellner, N.; Middendorf, R.; Muller, D.; Olcese, J. The human myometrium as a target for melatonin. J. Clin. Endocrinol. Metab, 2003, 88, 908-913.
188. Guney, M.; Oral, B.; Karahan, N.; Mungan, T. Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil. Steril., 2008, 89, 934-942.
189. Sanchez-Barcelo, E. J.; Mediavilla, M. D.; Tan, D. X.; Reiter, R. J. Clinical Uses of Melatonin: Evaluation of Human Trials. Curr. Med. Chem., 2010, 17, 2070-2095.