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Histochemistry and Cell Biology

, Volume 135, Issue 4, pp 389–396 | Cite as

Expression and cellular localizaion of melatonin-synthesizing enzymes in rat and human salivary glands

  • Masashi Shimozuma
  • Reiko Tokuyama
  • Seiko Tatehara
  • Hirochika Umeki
  • Shinji Ide
  • Kenji Mishima
  • Ichiro Saito
  • Kazuhito Satomura
Original Paper

Abstract

Melatonin, discovered in 1958, is secreted by the pineal gland primarily during the night. Its secretion is controlled by the light/dark cycle of the environment. Melatonin is also produced in and secreted by various extrapineal organs, tissues and cells and its synthesizing enzyme arylalkylamine N-acetyltransferase (AANAT) is expressed in various extrapineal organs, tissues and cells. Recently, it was reported that melatonin is present in saliva, but it is not certain where melatonin was synthesized and whether it was secreted into saliva and what function it may have in saliva. The present study was performed to investigate where melatonin was synthesized and whether it was secreted by salivary glands into saliva. We performed immunohistochemical analysis of the expression of AANAT in rat parotid, submandibular and sublingual glands and the expression of both AANAT and hydroxyindole-O-methyltransferase (HIOMT) in human submandibular glands. We evaluated the expression of AANAT and HIOMT mRNA in rat submandibular glands by quantitative reverse transcription-polymerase chain reaction. As a result, we observed expression of AANAT in epithelial cells of striated ducts in rat salivary glands and expression of AANAT, HIOMT and melatonin in epithelial cells of striated ducts in human submandibular glands. In addition, we also confirmed the expression of the most potent melatonin receptor, melatonin 1a receptor, in rat buccal mucosa. Our findings suggest that melatonin might be produced and secreted by salivary glands directly into saliva and that it might play some physiological role in the oral cavity.

Keywords

Melatonin Arylalkylamine N-acetyltransferase (AANAT) Hydroxyindole-O-methyltransferase (HIOMT) Salivary glands Melatonin 1a receptor Oral mucosa 

Notes

Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research (19390518, 21592575 and 22791986) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

References

  1. Adams JC (1981) Heavy metal intensification of DAB-based HRP reaction product. J Histochem Cytochem 29:775PubMedGoogle Scholar
  2. Aras HC, Ekström J (2008) Melatonin-evoked in vivo secretion of protein and amylase from the parotid gland of the anaesthetised rat. J Pineal Res 45:413–421PubMedCrossRefGoogle Scholar
  3. Axelrod J, Weissbach H (1960) Enzymatic O-methylation of N-acetylserotonin to melatonin. Science 29:312Google Scholar
  4. Barjavel MJ, Mamdouh Z, Raghbate N, Bakouche O (1998) Differential expression of the melatonin receptor in human monocytes. J Immunol 160:1191–1197PubMedGoogle Scholar
  5. Batmanabane M, Ramesh KG (1996) Effect of exogenous melatonin on the onset of puberty in female albino rats. Anet Rec 245:519–524CrossRefGoogle Scholar
  6. Carrillo-Vicoa P, Calvo JR, Abreu P, Lardone PJ, García-Mauriño S, Reiter RJ, Guerrero JM (2004) Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and/or paracrine substance. FASEB J 18:537–539Google Scholar
  7. Cevik-Aras H, Ekström J (2010) Anti-inflammatory action of cholecystokinin and melatonin in the rat parotid gland. Oral Dis 16:661–667PubMedCrossRefGoogle Scholar
  8. Cutando A, Galindo P, Gomez-Moreno G, Arana C, Bolaños J, Acuña-Castroviejo D, Wang HL (2006) Relationship between salivary melatonin and severity of periodontal diseases. J Periodontal 77:1533–1538CrossRefGoogle Scholar
  9. Cutando A, Gómez-Moreno G, Arana C, Acuña-Castroviejo D, Reiter RJ (2007) Melatonin: potential functions in the oral cavity. J Periodontol 78:1094–1102PubMedCrossRefGoogle Scholar
  10. Dollins AB, Zhdanova IV, Wurtman RJ, Lynch HJ, Deng MH (1994) Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc Natl Acad Sci USA 91:1824–1828PubMedCrossRefGoogle Scholar
  11. Esquifino AI, Villanua MA, Agarasal C (1987) Effect of neonatal melatonin administration on sexual development in the rat. J Steroid Biochem 27:1089–1093PubMedCrossRefGoogle Scholar
  12. Eşrefoğlu M, Seyhan M, Gül M, Parlakpinar H, Batçioğlu K, Uyumlu B (2005) Potent therapeutic effect of melatonin on aging skin in pinealectomized rats. J Pineal Res 39:231–317PubMedCrossRefGoogle Scholar
  13. Garcia-Mauriño S, Gonzalez-Haba MG, Calvo JR, Rafii-El-Idrissi M, Sanchez-Margalet V, Goberna R, Guerrero JM (1997) Melatonin enhances IL-2, IL-6, and IFN-gamma production by human circulating CD4 + cells: a possible nuclear receptor-mediated mechanism involving T helper type 1 lymphocytes and monocytes. J Immunol 159:574–581PubMedGoogle Scholar
  14. García-Mauriño S, Pozo D, Calvo JR, Guerrero JM (2000) Correlation between nuclear melatonin receptor expression and enhanced cytokine production in human lymphocytic and monocytic cell lines. J Pineal Res 29:129–137PubMedCrossRefGoogle Scholar
  15. Hamm HE, Menaker M (1980) Retinal rhythms in chicks: circadian variation in melantonin and serotonin N-acetyltransferase activity. Proc Natl Acad Sci 77:4998–5002PubMedCrossRefGoogle Scholar
  16. Hill SM, Blask DH (1988) Effects of the pineal hormone melatonin on the proliferation and morphological characteristics of human breast cancer cells (MCF-7) in culture. Cancer Res 48:6121–6126PubMedGoogle Scholar
  17. Itoh MT, Ishuzuka B, Kuribayashi Y, Amemiya A, Sumi Y (1999) Melatonin, its precursors, and synthesizing enzyme activities in the human ovary. Mol Hum Reprod 5:402–408PubMedCrossRefGoogle Scholar
  18. Itoh MT, Takahashi N, Abe M, Shimizu K (2007) Expression and cellular localization of melatonin-synthesizing enzymes in the rat lens. J Pineal Res 42:92–96PubMedCrossRefGoogle Scholar
  19. Kennaway DJ, Rowe SA (1995) Melatonin binding sites and their role in seasonal reproduction. J Reprod Fertil Suppl 49:423–435Google Scholar
  20. Kennaway DJ, Voultsios A (1998) Circadian rhythm of free melatonin in human plasma. J Clin Endocrinol Metab 83:1013–1015PubMedCrossRefGoogle Scholar
  21. Kimura S, Yonemura T, Kaya H (1993) Increased oxidative product formation by peripheral blood polymorphonuclear leukocytes in human periodontal disease. J Periodontal Res 28:197–203PubMedCrossRefGoogle Scholar
  22. Klain DC (2007) Arylalkylamine N-acetyltransferase: “the Timezyme”. J Biol Chem 282:4233–4237CrossRefGoogle Scholar
  23. Klein DC, Joan L (1970) Weller indole metabolism in the pineal gland: a circadian rhythm in N-acetyltransferase. Science 11:1093–1095CrossRefGoogle Scholar
  24. Kumasaka S, Shimozuma S, Kawamoto T, Misima K, Tokuyama R, Kamiya Y, Davaadori P, Saito I, Satomura K (2010) Possible involvement of melatonin in tooth development: expression of melatonin 1a receptor in human and mouse tooth germs. Histochem Cell Biol 133:577–584PubMedCrossRefGoogle Scholar
  25. Kvetnoy IM (1999) Extrapineal melatonin: location and role within diffuse neuroendocrine system. Histochem J 31:1–12PubMedCrossRefGoogle Scholar
  26. León J, Acuña-Castroviejo D, Escames G, Tan DX, Reiter RJ (2005) Melatonin mitigates mitochondrial malfunction. J Pineal Res 38:1–9PubMedCrossRefGoogle Scholar
  27. Lynch HJ, Brazezinski A, Deng MH, Lieberman HR, Wurtman RJ (1987) Effect of behavioural and physiological variables on melatonin secretion in humans. In: Fraschini F, Reiter RJ (eds) Advances in pineal resaerch, vol 2. Libbey, London, pp 181–190Google Scholar
  28. Martínez-Campa C, Alonso-González C, Mediavilla MD, Cos S, González A, Ramos S, Sánchez-Barceló EJ (2006) Melatonin inhibits both ER alpha activation and breast cancer cell proliferation induced by a metalloestrogen, cadmium. J Pineal Res 40:291–294PubMedCrossRefGoogle Scholar
  29. Mcarthur AJ, Hunt AE, Gillette MU (1997) Melatonin action and signal transduction in the rat suprachiasmatic circadian clock: activation of protein kinase C at dusk and dawn. Endocrinology 138:627–634PubMedCrossRefGoogle Scholar
  30. Rednab J, Armstrong S, Ng KT (1983) Free-running activity rhythms in the rat: entrainment by melatonin. Science 219:1089–1091CrossRefGoogle Scholar
  31. Reiter RJ (1991) Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev 12:151–180PubMedCrossRefGoogle Scholar
  32. Reiter RJ, Oh CS, Fujimori O (1996) Melatonin: its intracellular and genomic actions. Trends Endcrinol Metab 7:22–27CrossRefGoogle Scholar
  33. Reiter RJ, Tan DX, Manchester LC, Lopez-Burillo S, Sainz RM, Mayo JC (2003) Melatonin: detoxification of oxygen and nitrogen-based toxic reactants. Adv Exp Med Biol 527:539–548PubMedGoogle Scholar
  34. Roth JA, Kim BG, Lin WL, Cho MI (1999) Melatonin promotes osteoblast differentiation and bone formation. J Biol Chem 274:22041–22047PubMedCrossRefGoogle Scholar
  35. Sack RL, Brandes RW, Kendall AR, Lewy AJ (2000) Entrainment of free-running circadian rhythms by melatonin in blind people. N Engl Med 342:1070–1177CrossRefGoogle Scholar
  36. Satomura K, Tobiume S, Tokuyama R, Yamasaki Y, Kudou K, Maeda E, Nagayama M (2007) Melatonin at pharmacological doses enhances human osteoblastic differentiation in in vitro and promotes mouse cortical bone formation in vitro. J Pineal Res 42:231–239PubMedCrossRefGoogle Scholar
  37. Stefulj J, Hörtner M, Ghosh M, Schauenstein K, Rinner I, Wölfler A, Semmler J, Liebmann PM (2001) Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues of the rat. J Pineal Res 30:243–247PubMedCrossRefGoogle Scholar
  38. Ten Cate AR (1994) Oral histology, 4th edn. Mosby, St. Louis, pp 58–80Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Masashi Shimozuma
    • 1
  • Reiko Tokuyama
    • 1
  • Seiko Tatehara
    • 1
  • Hirochika Umeki
    • 1
  • Shinji Ide
    • 1
  • Kenji Mishima
    • 2
  • Ichiro Saito
    • 2
  • Kazuhito Satomura
    • 1
  1. 1.Second Department of Oral and Maxillofacial Surgery, Department of Oral Medicine and Stomatology, School of Dental MedicineTsurumi UniversityYokohamaJapan
  2. 2.Department of Pathology, School of Dental MedicineTsurumi UniversityYokohamaJapan

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