Cellular Localization of Prepro-Orexin and Orexin Receptors (Ox1R and Ox2R) in Merkel Cells

  • A. Beiras-Fernández
  • M. Blanco
  • T. García-Caballero
  • R. Gallego
  • C. Diéguez
  • A. Beiras
Conference paper

Summary

Orexins (A and B) were first demonstrated in neurons of the lateral hypothalamus, both peptides derived from a common precursor called prepro-orexin. Orexins act through previously orphan G-protein receptors named orexin receptor 1 (Ox1R) and orexin receptor 2 (Ox2R). Up to the present, various neuropeptides have been detected in neuroendocrine cells of the skin (Merkel cells). The aim of our study was to investigate the presence of orexin receptors and prepro-orexins in Merkel cells. Immunohistochemical techniques were performed to detect preproorexin and orexin receptors (Ox1R and Ox2R) in human and porcine Merkel cells. Prepro-orexin was expressed in the cytoplasm of Merkel cells of pig snout skin and human fingertip. Immunoreactivity for prepro-orexin was more intense in the mature side of the Merkel cell. Epidermal nerve terminals associated with Merkel cells and dermal nerve fibers showed no immunostaining. Orexin receptors were also demonstrated in the Merkel cells of pig snout skin. Further studies must be followed to ascertain the role that orexins play in cutaneous neuroendocrine cells.

Keywords

Citrate Cortisol Serotonin Polypeptide Paraffin 

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References

  1. Beiras A, Garcia-Caballero T, Espinosa J, Gallego R (1986) Staining of Merkel cells of pig snout epidermis using the uranaffin reaction. Morphometric analysis of neuroendocrine granules. Differentiation 32: 89–92CrossRefGoogle Scholar
  2. Beiras A, Garcia-Caballero T, Fernandez Redondo V, Gallego R (1987) Morphometric characterization of the human neuroendocrine Merkel cells. J Invest Dermatol 88: 766–768PubMedCrossRefGoogle Scholar
  3. Blanco M, Lopez M, Garcia-Caballero T, Gallego R, Vazquez-Boquete A, Morel G, Senaris R, Casanueva F, Dieguez C, Beiras A (2001) Cellular localization of orexin receptors in human pituitary. J Clin Endocrin Metabol 86: 1616–1619CrossRefGoogle Scholar
  4. Date Y, Ueta Y, Yamashita H, Yamaguchi H, Matsukura S, Kangawa K, Sakurai T, Yanagisawa m, Nakazato M (1999) Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. Proc Natl Acad Sci USA 96: 748–753PubMedCrossRefGoogle Scholar
  5. De Lecea L, Kilduff TS, Peyron C, Gao XB, Foye P, Danielson PE, Fukuhara C, Battemberg E, Gautvik VT, Bartlett II FS, Frankel VN, Van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 95: 322–327PubMedCrossRefGoogle Scholar
  6. Dube MG, Kalra SP, Kalra P (1999) Food intake elicited by central administration of orexins/hypocretins: identification of hypothalamic sites of action. Brain Res 842: 473–477PubMedCrossRefGoogle Scholar
  7. Gu J, Polak JM, Noorden SW, Pearse AGE, Marangos PZ, Azzopardi JG (1983) Immunostaining of neuron-specific enolase as a diagnostic tool for Merkel cell tumours. Cancer 52: 1039–1043PubMedCrossRefGoogle Scholar
  8. Ichinose M, Asai M, Sawada M, Sasaki K, Oomura Y (1998) Induction of outward current by Orexin-B in mouse peritoneal macrophages. FEBS Lett 440: 51–54PubMedCrossRefGoogle Scholar
  9. Jöhren O, Neidert SJ, Kummer M, Dendorfer A, Dominiak P (2001) Preproorexin and orexin receptors mRNAs are differentially expressed in peripheral tissues of male and female rats. Endocrinology 142: 3324–3331PubMedCrossRefGoogle Scholar
  10. Lopez M, Señaris R, Gallego R, Garcia-Caballero T, Lago F, Seoane L, Casanueva F, Dieguez C (1999) Orexin receptors are expressed in the adrenal medulla of the rat. Endocrinology 140: 5991–5994PubMedCrossRefGoogle Scholar
  11. Mazzochi G, Malendowiez LK, Gottardo L, Aragona F, Nussdorfer GG (2001) Orexin-A stimulates cortisol secretion from human adrenocortical cells through activation of the adenylate cyclase-dependent signalling cascade. J Clin Endocrinol Metab 86: 778–782CrossRefGoogle Scholar
  12. Moll R, Moll I, Franke WW (1984) Identification of Merkel cells in human skin by specific cytokeratin antibodies: changes of cell density and distribution in fetal and adult plantar epidermis. Differentiation 28: 136–154PubMedCrossRefGoogle Scholar
  13. Ness KH, Morton TH, Dale BA (1987) Identification of Merkel cells in oral epithelium using antikeratin and antineuroendocrime monoclonal antibodies. J Dent Res 88: 1154–1158Google Scholar
  14. Ortonne JP, Darmon M (1985) Merkel cells express desmosomal proteins and cytokeratines. Acta Derm Venereol 65: 161–164PubMedGoogle Scholar
  15. Ortonne JP, Petchot-Bacque JP, Verrando P, Pisani A, Pautrat G, Bernerd F (1988) Normal Merkel cells express a synaptophysin-like immunoreactivity. Dermatologica 177: 1–10PubMedCrossRefGoogle Scholar
  16. Peyron C, Tighe DK, Van den Pol AN, de Lecea L, Heller HC, Sutcliffe JC, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal system. J Neurosci 18: 9996–10015PubMedGoogle Scholar
  17. Piper DC, Upton N, Smith MI, Hunter AJ (2000) The novel brain neuropeptides, orexin-A, modulates the sleep-wake cycle in rats. Eur J Neurosci 12: 726–730PubMedCrossRefGoogle Scholar
  18. Sakurai T (2002) Roles of orexins in regulation of feeding and wakefulness. Neuroreport 13: 987–995PubMedCrossRefGoogle Scholar
  19. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JRS, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Tenet JA, Elshourbagy NA, Bergsma DJ, Yanasinawa M (1998) Orexins and orexins receptors: a family of hypothalamic neuropeptides and G-coupled protein receptors that regulate feeding behaviour. Cell 92: 573–585PubMedCrossRefGoogle Scholar
  20. Saurat J, Merot Y, Didierjean L, Dahl D (1984) Normal rabbit Merkel cells do not express neurofilament proteins. J Invest Dermatol 82: 641–642PubMedCrossRefGoogle Scholar
  21. Tachibana T (1995) The Merkel cell: recent findings and unresolved problems. Arch Histol Cytol 58: 379–396PubMedCrossRefGoogle Scholar
  22. Taheri S, Zeitzer JM, Mignot E. (2002) The role of hypocretins (orexins) in sleep regulation and narcolepsy. Annu Rev Neurosci 25: 283–313PubMedCrossRefGoogle Scholar
  23. Takahashi N, Okumura T, Yamada H, Kohgo Y (1999) Stimulation of gastric acid secretion by centrally administered Orexin-A in conscious rats. Biochem Biophys Res Commun 254: 653–657CrossRefGoogle Scholar
  24. Van den Pol AN (1999) Hypothalamic hypocretin (orexin): robust inervation of the spinal cord. J Neurosci 19: 3171–3182PubMedGoogle Scholar
  25. Van den Pol AN, Gao XB, Obrietan K, Kilduff TS, Belousov AB (1998) Presynaptic and postsynaptic actions and modulation of neuroendocrine neurons by a new hypothalamic peptid: hypocretin/orexin. J Neurosci 18: 7962–7971PubMedGoogle Scholar
  26. Zaccone G (1986) Neuron-specific enolase and serotonin in the Merkel cells of conger-eel (Conger conger) epidermis. An immunohistochemical study. Histochemistry 85: 29–34PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • A. Beiras-Fernández
    • 1
  • M. Blanco
    • 1
  • T. García-Caballero
    • 1
  • R. Gallego
    • 1
  • C. Diéguez
    • 2
  • A. Beiras
    • 1
  1. 1.Department of Morphological Sciences, Faculty of MedicineUniversity of Santiago de CompostelaSpain
  2. 2.Department of Physiology, Faculty of MedicineUniversity of Santiago de CompostelaSpain

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