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Calcitonin gene-related peptide (CGRP) immunoreactivity in the neuroendocrine Merkel cells and nerve fibres of pig and human skin

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Summary

The presence of calcitonin gene-related peptide (CGRP) in the skin of pig snout and human fingertip was investigated using immunohistochemical techniques. CGRP immunoreactivity was found in Merkel cells and nerve fibres of both species. In pig snout skin, Merkel cells containing CGRP were seen forming clusters at the tips of rete ridge epidermis and in the external root sheath of sinus hair follicles (vibrissae). Human Merkel cells immunostained for CGRP were found isolated or forming small groups in the basal layer of glandular epidermal ridges. In all cases, immunoreactivity was more intense on the side of the Merkel cell facing the associated nerve terminal (which was never positive for CGRP). This part of the Merkel cell has the greatest density of dense-cored granules, suggesting that CGRP must be stored in these granules. Nerve, bundles containing CGRP-immunoreactive fibres were found at dermal and hypodermal level, and blood vessels were often surrounded by CGRP nerve fibres. In pig snout skin some nerve fibres containing CGRP penetrated the epidermis and terminated as free endings, and in the human fingertip a small number of CGRP-immunoreactive nerve fibres were seen in Meissner's corpuscles.

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References

  • Alvarez FJ, Cervantes C, Blasco I, Villalba R, Martinez-Murillo R, Polak JM, Rodrigo J (1988a) Presence of calcitonin generelated peptide (CGRP) and substance P (SP) immunoreactivity in intraepidermal free nerve endings of cat skin. Brain Res 442:391–395

    Google Scholar 

  • Alvarez FJ, Cervantes C, Villalba R, Blasco I, Polak JM, Rodrigo J (1988b) Immunocytochemical analysis of calcitonin gene-related peptide and vasoactive intestinal polypeptide in cat Merkel cells and cutaneous free nerve endings: light and electron microscopic study. Cell Tissue Res 254:429–437

    Google Scholar 

  • Amara SG, Jonas V, Rosenfeld MG, Ong ES, Evans RM (1982) Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature 298:240–244

    Google Scholar 

  • Brain SD, Williams TJ, Tippins JR, Morris HR, MacIntyre I (1985) Calcitonin gene-related peptide is a potent vasodilator. Nature 313:54–56

    Google Scholar 

  • Bonnard C, Papermaster DS, Kraehenbuhl JP (1984) The streptavidin-biotin bridge technique: application in light and electron microscope immunocytochemistry. In: Polak JM, Varndell IM (eds) Immunolabelling for electron microscopy. Elsevier Science, Amsterdam, pp 95–111

    Google Scholar 

  • Cadieux A, Springall DR, Mulderry K, Rodrigo J, Ghatei MA, Terenghi G, Bloom SR, Polak JM (1986) Occurrence, distribution and ontogeny of CGRP immunoreactivity in the rat lower respiratory tract: effect of capsaicin treatment and surgical denervations Neuroscience 19:605–627

    Google Scholar 

  • Dalsgaard CJ, Jonsson CE, Hökfelt T, Cuello AC (1983) Localization of substance P-immunoreactive nerve fibres in the human digital skin. Experientia 39:1018–1020

    Google Scholar 

  • Diamond J, Holmes M, Nurse CA (1986) Are Merkel cell-neurite reciprocal synapses involved in the initiation of tactile responses in salamander skin?. J Physiol (Lond) 376:101–120

    Google Scholar 

  • García-Caballero T, Cuevas J, Gallego R, Rosón E, Forteza J, Beiras A (1989) Synaptophysin-like immunoreactivity in te Merkel cells of the pig snout skin. Ultrastruct Pathol 13:55–61

    Google Scholar 

  • Gibson SJ, Polak JM, Bloom SR, Sabata IM, Mulderry PM, Ghatei MA, McGregor GP, Morrison JFB, Kelly JS, Evans RM, Rosenfeld MG (1984) Calcitonin gene-related peptide immunoreactivity in the spinal cord of man and of eight other species. J Neurosci 4:3101–3111

    Google Scholar 

  • Gottschaldt KM, Vahle-Hinz C (1981) Merkel cell receptors: Structure and transducer function. Science 214:183–186

    Google Scholar 

  • Gottschaldt KM, Vahle-Hinz C (1982) Evidence against transmitter function of met-enkephalin and chemosynaptic impulse generation in “Merkel cell” mechanorreceptor: Exp Brain Res 45:459–463

    Google Scholar 

  • Gu J, Polak JM, Noorden SV, Pearse AGE, Marangos PJ, Azzopardi JG (1983) Immunostaining of neuron-specific enolase as a diagnostic tool for Merkel cell tumors. Cancer 52:1039–1043

    Google Scholar 

  • Halata Z, Munger BL (1983) The sensory innervation of primate facial skin. II. Vermillion border and mucosa of lip. Brain Res Rev 5:81–107

    Google Scholar 

  • Håkanson R, Sundler F (1983) The design of the neuroendocrine system: a unifying concept and its consequences. Trends Pharmacol Sci 4:41–44

    Google Scholar 

  • Hartschuh W, Weihe E (1980) Fine structural analysis of the synaptic junction of Merkel cell axon-complexes. J Invest Dermatol 75:159–165

    Google Scholar 

  • Hartschuh W, Weihe E, Büchler M, Helmstaedter V, Feurle GE, Forssmann WG (1979) Met-enkephalin-like immunoreactivity in Merkel cells. Cell Tissue Res 201:343–348

    Google Scholar 

  • Hartschuh W, Weihe E, Büchler M (1980) Met-enkephalin-like immunoreactivity in Merkel cells of various species (Abstract). J Invest Dermatol 74:453

    Google Scholar 

  • Hartschuh W, Weihe E, Yanaihara N, Reinecke M (1983) Immunohistochemical localization of vasoactive intestinal polypeptide (VIP) in Merkel cells of various mammals: evidence for a neuromodulator function of the Merkel cell. J Invest Dermatol 81:361–364

    Google Scholar 

  • Hartschuh W, Reinecke M, Weihe E, Yanaihara N (1984) VIP-immunoreactivity in the skin of various mammals: immunohistochemical, radioimmunological and experimental evidence for a dual localization in cutaneous nerves and Merkel cells. Peptides 5:239–245

    Google Scholar 

  • Kameda Y (1987) Localization of immunoreactive calcitonin generelated peptide in thyroid C cells from various mammalian species. Anat Rec 219:204–212

    Google Scholar 

  • Kawai Y, Takami K, Shiosaka S, Emson PC, Hillyard CJ, Girgis S, MacIntyre I, Tohyama M (1985) Topographic localization of calcitonin gene-related peptide in the rat brain: an immunohistochemical analysis. Neuroscience 15:747–763

    Google Scholar 

  • Kuramoto H, Kondo H, Fujita T (1987) Calcitonin gene-related peptide (CGRP)-like immunoreactivity in scattered chromaffin cells and nerve fibers in the adrenal gland of rats. Cell Tissue Res 247:309–315

    Google Scholar 

  • Lauweryns JM, Van Ranst L (1987) Calcitonin gene-related peptide immunoreactivity in rat lung: light and electron microscopic study. Thorax 42:183–189

    Google Scholar 

  • Merkel F (1875) Tastzellen und Tastkörperchen bei den Haustieren und beim Menschen. Arch Mikrosk Anat 11:636–652

    Google Scholar 

  • 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 28:136–154

    Google Scholar 

  • Munger BL (1965) The intraepidermal innervation of snoutskin of the opossum: a light and electron microscopic study with observations on the nature of Merkel's Tastzellen. J Cell Biol 26:79–96

    Google Scholar 

  • Munger BL, Pubols LM, Pubols BH (1971) The Merkel rete papilla, a slowly adapting sensory receptor in mammalian glabrous skin. Brain Res 29:47–61

    Google Scholar 

  • Ness KH, Morton TH, Dale BA (1987) Identification of Merkel cells in oral epithelium using antikeratin and antineuroendocrine monoclonal antibodies. J Dent Res 66:1154–1158

    Google Scholar 

  • Ortonne JP, Darmon M (1985) Merkel cells express desmosomal proteins and cytokeratins. Acta Derm Venereol (Stockh) 65:161–164

    Google Scholar 

  • 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):1–10

    Google Scholar 

  • O'Shaughnessy DJ, McGregor GP, Ghatei MA, Blank MA, Springall DR, Gu J, Polak JM, Bloom SR (1983) Distribution of bombesin, somatostatin, substance P and vasoactive intestinal polypeptide in feline and porcine skin. Life Sci 32:2827–2836

    Google Scholar 

  • Rodrigo J, Polak JM, Fernandez L, Ghatei MA, Mulderry P, Bloom SR (1985a) Calcitonin gene-related peptide immunoreactive sensory and motor nerves of the rat, cat and monkey esophagus. Gastroenterology 88:444–451

    Google Scholar 

  • Rodrigo J, Polak JM, Terenghi G, Cervantes C, Ghatei MA, Mulderry PK, Bloom SR (1985b) Calcitonin gene-related peptide (CGRP)-immunoreactive sensory and motor nerves of the mammalian palate. Histochemistry 82:62–74

    Google Scholar 

  • Rosenfeld MG, Mermod JJ, Amara SG, Swanson LW, Sawchenko PE, Rivier J, Vale WW, Evans RM (1983) Production of a novel neuropeptide encoded by the calcitonin gene via tissuespecific RNA processing. Nature 304:129–135

    Google Scholar 

  • Saurat JH, Chavaz P, Carraux P, Didierjean L (1983) A human monoclonal antibody reacting with Merkel cells: immunofluorescence, immunoperoxidase and immunoelectron microscopy. J Invest Dermatol 81:249–253

    Google Scholar 

  • Saurat JH, Didirjean L, Skalli O, Siegenthaler G, Gabbiani G (1984) The intermediate filament proteins of rabbit normal epidermal Merkel cells are cytokeratins. J Invest Dermatol 83:431–435

    Google Scholar 

  • Scheuermann DW, Timmermans JP, Adriaensen D, De Groodt-Lasscel MHA (1987) Immunoreactivity for calcitonin gene-related peptide in neuroepithelial bodies of the newborn cat. Cell Tissue Res 249:337–340

    Google Scholar 

  • Smith KR Jr (1977) The Haarscheibe. J Invest Dermatol 69:68–74

    Google Scholar 

  • Tachibana T, Ishizeki K, Sakakura Y, Nawa T (1984) Ultrastructural evidence for a possible secretory function of Merkel cells in the barbels of a teleost fish, Cyprinus carpio. Cell Tissue Res 235:695–697

    Google Scholar 

  • Terenghi G, Polak JM, Ghatei MA, Mulderry PK, Butler JM, Unger WG, Bloom SR (1985) Distribution and origin of calcitonin gene-related peptide (CGRP) immunoreactivity in the sensory innervation of the mammalian eye. J Comp Neurol 233:506–516

    Google Scholar 

  • Uddmann R, Edvinsson L, Ekblad E, Håkanson R, Sundler F (1986) Calcitonin gene-related peptide (CGRP): perivascular distribution and vasodilatory effects. Regul Peptides 15:1–23

    Google Scholar 

  • Warner TFCS, Uno H, Hafez GR, Burgess J, Bolles C, Lloyd RV, Oka M (1983) Merkel cell and Merkel cells tumors: ultrastructure, immunocytochemistry and review of the literature. Cancer 52:238–245

    Google Scholar 

  • Zaccone G (1986) Neuron-specific enolase and serotonin in the Merkel cells of conger-eel (Conger conger) epidermis. An immunohistochemical study. Histochemistry 85:29–34

    Google Scholar 

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García-Caballero, T., Gallego, R., Rosón, E. et al. Calcitonin gene-related peptide (CGRP) immunoreactivity in the neuroendocrine Merkel cells and nerve fibres of pig and human skin. Histochemistry 92, 127–132 (1989). https://doi.org/10.1007/BF00490231

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  • DOI: https://doi.org/10.1007/BF00490231

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