Summary
The epithelium of the airways is rich in endocrine cells containing serotonin and/or a wide variety of regulatory peptides. These cells usually occur in clusters in the lungs but are also found scattered in the larynx and trachea. In the present study, endocrine cells in the airways of mouse, rat, hamster, guinea pig, pig, sheep and squirrel monkey were examined for the presence of serotonin, helodermin-like peptides and other regulatory peptides using immunocytochemistry and radioimmunoassay. In addition, we looked for the protein gene product 9.5 (PGP), which occurs in many peptide hormone-producing endocrine cells in the body. Both clustered and scattered endocrine cells in the airways were found to display coexistence of serotonin and peptides, such as a helodermin-like peptide, calcitonin and calcitonin gene-related peptide (CGRP). The PGP-immunoreactive cells were numerous and included elements containing serotonin and/or regulatory peptides. An additional PGP-immunoreactive endocrine cell population lacked serotonin and regulatory peptides. Helodermin-immunoreactive material was demonstrated in endocrine cells of the airways in the mouse and hamster but not in any of the other species studied. Serotonin was an endocrine cell constituent in all the species studied. Calcitonin and CGRP could be demonstrated by immunocytochemistry in the mouse, rat, and hamster, but not in the guinea pig, sheep, pig and monkey. In the hamster airways double immunostaining indicated that the helodermin-like peptide occurred in a subpopulation of the CGRP- and serotonin-containing cells. Most of the CGRP-containing cells stored serotonin; some of them also contained calcitonin. The chemical coding of these cells resembled that of the thyroid C cells.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Biartell A, Persson P, Absood A, Sundler F, Håkanson R (1989) Helodermin-like peptides in noradrenaline cells of adrenal medulla. Regul Pept 26:27–34
Cadieux A, Springall DR, Mulderry PK, 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
Costa M, Furness JB, Gibbins IL (1986) Chemical coding of enteric neurons. Prog Brain Res 68:217–239
Cutz E, Gillan JE, Track NS (1984) Purmonary endocrine cells in the developing human lung and during neonatal adaptation. In: Becker KL, Gazdar AF (eds) The endocrine lung in health and disease. Saunders, Philadelphia, pp 210–231
Dayer AM, De Mey J, Will JA (1985) Localization of somatostatin-, bombesin-, and serotonin-like immunoreactivity in the lung of the fetal rhesus monkey. Cell Tissue Res 239:621–625
Ericson LE, Håkanson R, Larsson B, Owman C, Sundler F (1972) Fluorescence and electron microscopy of amine-storing enterochromaffin like cells in tracheal epithelium of mouse. Z Zellforsch 124:532–545
Ghatei MA, Sheppard MN, O'Shaughnessy DJ, Adrian TE, McGregor GP, Polak JM, Bloom SR (1982) Regulatory peptides in the mammalian respiratory tract. Endocrinology 111:1248–1254
Gosney JR, Sissons MCJ (1985) Widespread distribution of bronchopulmonary endocrine cells immunoreactive for calcitonin in the lung of the normal adult rat. Thorax 40:194–198
Grunditz T, Håkanson R, Hedge G, Rerup C, Sundler F, Uddman R (1986a) Peptide histidine isoleucine amide stimulates thyroid hormone secretion and coexists with vasoactive intestinal polypeptide in intrathyroid nerve fibers from larygeal ganglia. Endocrinology 118:783–790
Grunditz T, Ekman R, Håkanson R, Rerup C, Sundler F, Uddman R (1986b) Calcitonin gene-related peptide in thyroid nerve fibers and C-cells: effects on thyroid hormone secretion and response to hypercalcemia. Endocrinology 119:2313–2324
Grunditz T, Persson P, Håkanson R, Absood A, Böttcher G, Rerup C, Sundler F (1989) Helodermin-like peptides in thyroid C cells. Stimulation of thyroid hormone secretion and suppression of calcium incorporation in bone. Proc Natl Acad Sci USA 86:1357–1361
Hage E (1973) Electron microscopic identification of several types of endocrine cells in the bronchial epithelium of human foetuses. Z Zellforsch 141: 401–412
Johnson DE, Wobken JD (1987) Calcitonin gene-related peptide immunoreactivity in airway epithelial cells of human fetus and infant. Cell Tissue Res 250:579–583
Kameya T, Bessho T, Tsumuraya M, Yamaguchi K, Abe K, Shimosato Y, Yanaihara N (1983) Production of gastrin releasing peptide by medullary carcinoma of the thyroid. An immunohistochemical study. Virchews Arch [A] 401:99–108
Keith IM, Ekman R (1988) Calcitonin gene-related peptide in hamster lung and its co-existence with serotonin: a chemical and immunocytochemical study. Regul Pept 22:315–325
Kivipelto L, Absood A, Håkanson R, Sundler F, Panula P (1991) Helodermin- and helospectin-like immunoreactivity in the rat brain; an immunochemical and immunohistochemical study. Neuroscience (in press)
Lauweryns JM, Van Ranst L (1988) Protein gene product 9.5 expression in the lungs of humans and other mammals. Immunocytochemical detection in neuroepithelial bodies, neuroendocrine cells and nerves. Neurosci Lett 85:311–316
Lauweryns JM, Cokelaere M, Theunynck P (1972) Neuro-epithelial bodies in the respiratory mucosa of various mammals — a light optical, histochemical, and ultrastructural investigation. Z Zellforsch 135:569–592
Lauweryns JM, Bock V de, Verhofstad AAJ, Steinbusch HWM (1982) Immunohistochemical localization of serotonin in intrapulmonary neuro-epithelial bodies. Cell Tissue Res 226:215–223
Lauweryns JM, Bock V de, Guelinckx P, Decramer M (1983) Effects of unilateral hypoxia on neuroepithelial bodies in rabbit lungs. J Appl Physiol 55:1665–1668
Marchevsky AM, Kleinerman J (1983) Quantitative and immunocytochemical studies of APUD cells in airways and gut. The effects of priming with L-DOPA and 5-HTP. Lung 161:67–76
Mårtensson H, Böttcher G, Hambraeus G, Sundler F, Willén H, Nobin A (1987) Bronchial carcinoids: an analysis of 91 cases. World J Surg 11:356–364
McDonald TJ, Jörnvall H, Nilsson G, Vagne M, Ghatei M, Bloom SR, Mutt V (1979) Characterization of gastrin releasing peptide from non-antral gastric tissue. Biochem Biophys Res Commun 90:227–233
Parker DS, Raufman J-P, O'Donohue TL, Bledsoe M, Yoshida H, Pisano JJ (1984) Amino acid sequences of helospectins, new members of the glucagon super-family found in Gila monster venom. J Biol Chem 259:11751–11755
Scheuermann DW, Timmermans J-P, Adriaensen D, De Groodt-Lasseel MHA (1987) Immunoreactivity for calcitonin gene-related peptide in neuroepithelial bodies of the newborn cat. Cell Tissue Res 249:337–340
Sorokin SP, Hoyt RF, Grant MM (1982) Development of neuroepithelial bodies in fetal rabbit lungs. I. Appearance and functional maturation as demonstrated by high-resolution light microscopy and formaldehyde-induced fluorescence. Exp Lung Res 3:237–259
Sorokin SP, Hoyt F, Pearsall AD (1983) Comparative biology of small granule cells and neuroepithelial bodies in the respiratory system. Am Rev Respir Dis 128:S26-S31
Sundler F, Brodin E, Ekblad E, Håkanson R, Uddman R (1985) Sensory nerve fibers: distribution of substance P, neurokinin A, and calcitonin gene-related peptide. In: Håkanson R, Sundler F (eds) Tachykinin antagonists. Elsevier, Amsterdam, pp 3–14
Sundler F, Christophe J, Robberecht P, Yanaihara N, Yanaihara C, Grunditz T, Håkanson R (1988) Is helodermin produced by medullary thyroid carcinoma cells and normal C-cells? Immunocytochemical evidence. Regul Pept 20:83–89
Thompson RJ, Doran JF, Jackson P, Dhillon AP, Rode J (1983) PGP 9.5 — a new marker for vertebrate neurons and neuroendocrine cells. Brain Res 278:224–228
Tsutsumi Y, Osamura RY, Watanabe K, Yanaihara N (1983) Simultaneous immunohistochemical localization of gastrin releasing peptide (GRP) and calcitonin (CT) in human bronchial endocrine-type cells. Virchows Arch [A] 400:163–171
Uddman R, Luts A, Sundler F (1985) Occurrence and distribution of calcitonin gene-related peptide in the mammalian respiratory tract and middle ear. Cell Tissue Res 241:551–555
Vandermeers A, Vandermeers-Piret MC, Robberecht P, Waelbroeck M, Dehaye J-P, Winand J, Christophe J (1984) Purification of a novel pancreatic secretory factor (PSF) and a novel peptide with VIP- and secretin-like properties (helodermin) from Gila monster venom. FEBS Lett 166:273–276
Vandermeers A, Gourlet P, Vandermeer-Piret M-C, Cauvin A, De Neef P, Rathe J, Svoboda M, Robberecht P, Christophe J (1987) Chemical, immunological and biological properties of peptides like vasoactive-intestinal-peptide and peptide-histidine-isoleucinamide extracted from the venom of two lizards (Heloderma horridum and Heloderma suspectum). Eur J Biochem 164:321–327
Wharton J, Polak JM, Bloom SR, Ghatei MA, Solcia E, Brown MR, Pearse AGE (1978) Bombesin-like immunoreactivity in the lung. Nature 273:769–770
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Luts, A., Uddman, R., Absood, A. et al. Chemical coding of endocrine cells of the airways: presence of helodermin-like peptides. Cell Tissue Res 265, 425–433 (1991). https://doi.org/10.1007/BF00340865
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00340865