Skip to main content
SpringerLink
Log in

Calcitonin gene-related peptide and its mRNA in pulmonary neuroendocrine cells and ganglia

  • Published:
Histochemistry Aims and scope Submit manuscript

Summary

The occurrence of calcitonin gene-related peptide (CGRP) and it's mRNA was studied in lungs of rats and piglets using in situ hybridization with two synthetic oligonucleotide probes followed by immunocytochemistry (ICC). CGRP mRNA was present in pulmonary neuroendocrine cells (PNEC) of both the solitary type and cluster type (neuroepithelial body; NEB) at all levels of the airway epithelium from bronchi to alveoli. The distribution of labelled cells was similar to that previously described with ICC. The 44-mer probe provided stronger hybridization signal than the 34-mer and the two combined increased labelling slightly. Formalin fixation reduced labelling and tended to increase background. Labelling for CGRP mRNA was evenly distributed over the cytoplasm, whereas CGRP-like immunoreactivity (LI) usually was of highest intensity toward the base of the PNEC, suggesting basal accumulation of synthesized peptide. CGRP-LI was also observed in occasional rat ganglia and in some, but not all, piglet ganglia. These local neurons may contribute to the CGRP fibers of airways and vasculature, and could theoretically bridge their dendrites and axons between NEB and the effector organ (e.g. artery or arteriole) thus accomplishing a function similar to the postulated axon reflex.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

    Google Scholar 

  • Amara SG, Evans RM, Rosenfeld MG (1984) Calcitonin/calcitonin gene-related peptide transcription unit: tissue-specific expression involves selective use of alternative polyadenylation sites. Mol Cell Biol 4:2151–2160

    Google Scholar 

  • Barnes PJ (1989) Airway neuropeptides: roles in fine tuning and in disease. NIPS 4:116–120

    Google Scholar 

  • 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

    Google Scholar 

  • Dalsgaard CJ, Lundberg JM (1984) Evidence for a spinal afferent innervation of the guinea pig lower respiratory tract as studied by the horseradish peroxidase technique. Neurosci Lett 45:117–122

    Google Scholar 

  • Edbrooke MR, Parker D, McVey JH, Riley JH, Sorenson GD, Pettengill OS, Craig RK (1958) Expression of the human calcitonin/CGRP gene in lung and thyroid carcinoma. EMBO J 4:715–724

    Google Scholar 

  • Goltzman D, Mitchell J (1985) Interaction of calcitonin and calcitonin gene-related peptide at receptor sites in target tissues. Science 227:1343–1345

    Google Scholar 

  • Ghatei MA, Springall DR, Richards IM, Oostveen JA, Griffin RL, Cadieux A, Polak JM, Bloom SR (1987) Regulatory peptides in the respiratory tract of Macaca fascicularis. Thorax 42:431–439

    Google Scholar 

  • Hoppener JWM, Steenbergh PH, Moonen PJJ, Wagenaar SJSC, Jansz HS, Lips CJM (1986) Detection of mRNA encoding calcitonin, calcitonin gene-related peptide and proopiomelanocortin in human tumors. Mol Cell Endocrinol 47:125–130

    Google Scholar 

  • Keith IM, Ekman R (1988) Calcitonin gene-related peptide in hamster lung and its coexistence with serotonin: a chemical and immunocytochemical study. Regul Pept 22:315–323

    Google Scholar 

  • Keith IM, Ekman R (1991) Dynamic aspects of regulatory peptides in chronic hypoxic pulmonary hypertension. Exp Lung Res (in press)

  • Keith IM, Ekman R (1990) Peptide YY-like material and its spatial relationship with NPY, CGRP and 5-HT in the lung of the Syrian golden Hamster. Cell Tissue Res 262:543–550

    Google Scholar 

  • Keith IM, Will JA (1981) Hypoxia and the neonatal rabbit lung: neuroendocrine cell numbers, 5-HT fluorescence intensity, and the relationship to arterial thickness. Thorax 36:767–773

    Google Scholar 

  • Keith IM, Wiley L, Will JA (1981) Pulmonary neuroendocrine cells: Decreased serotonin fluorescence and stable argyrophilcell numbers in acute hypoxia. Cell Tissue Res 214:201–205

    Google Scholar 

  • Lauweryns JM, Van Lommel A (1986) Effect of various vagotomy procedures on the reaction to hypoxia of rabbit neuroepithelial bodies: modulation by intrapulmonary axon reflexes? Exp Lung Res 11:319–339

    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 

  • Lauweryns JM, Cokelaere M, Deelersnyder M, Liebens M (1977) Intrapulmonary neuro-epithelial bodies in newborn rabbits. Influence of hypoxia, hyperoxia, hypercapnia, nicotine, reserpine, L-DOPA, and 5-HTP. Cell Tissue Res 182:425–440

    Google Scholar 

  • Lauweryns JM, Cokelaere M, Lerut T, Theunynck P (1978) Cross-circulation studies on the influence of hypoxia and hypoxemia on neuro-epithelial bodies in young rabbits. Cell Tissue Res 193:373–386

    Google Scholar 

  • Leff SE, Evans RM, Rosenfeld MG (1987) Splice commitment dictates neuron-specific alternative RNA processing in calcitonin/CGRP gene expression. Cell 48:517–524

    Google Scholar 

  • Lisney SJW, Bharali LAM (1989) The axon reflex: an outdated idea or a valid hypothesis? NIPS 4:45–48

    Google Scholar 

  • Lundberg JM, Franco-Cereda A, Hua X-Y, Hökfelt T, Fischer J (1985) Co-existence of substance P and calcitonin gene-related peptide immunoreactivities in sensory nerves in relation to cardiovascular and bronchoconstrictor effects of capsaicin. Eur J Pharmacol 108:315–319

    Google Scholar 

  • Martling C-R, Saria A, Fischer JA, Hökfelt T, Lundberg JM (1988) Calcitonin gene-related peptide and the lung: neuronal co-existence with substance P, release by capsaicin and vasodilatory effect. Regul Pept 20:125–139

    Google Scholar 

  • Nelkin BD, Rosenfeld KI, de Bustros A, Leong SS, Roos BA, Baylin BS (1984) Structure and expression of a gene encoding human calcitonin and calcitonin gene related peptide. Biochem Biophys Res Commun 123:648–655

    Google Scholar 

  • Palmer JBD, Cuss FMC, Mulderry PK, Ghatei MA, Springall DR, Cadieux A, Bloom S, Polak J (1987) Calcitonin gene-related peptide is localized to human airway nerves and potently constricts human airway smooth muscle. Br J Pharmacol 91:95–101

    Google Scholar 

  • Polak JM, Bloom SR (1985) Occurrence and distribution of regulatory peptides in the respiratory tract. Recent Res Cancer Res 99:1–16

    Google Scholar 

  • Rethelyi M, Meth CB, Lund PK (1989) Distribution of neurons expressing calcitonin gene-related peptide mRNAs in the brain stem, spinal cord and dorsal root ganglia of rat and guinea-pig. Neurosci Lett 29:225–239

    Google Scholar 

  • Riley JH, Edbrooke MR, Craig RK (1986) Ectopic synthesis of high-Mr calcitonin by the BEN lung carcinoma cell line reflects aberrant proteolytic processing. FEBS Lett 198:71–79

    Google Scholar 

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

    Google Scholar 

  • Rosenfeld MG, Amara SG, Evans RM (1984) Alternative RNA processing: determining neuronal phenotype. Science 225:1315–1320

    Google Scholar 

  • Schalling M, Dagerlind Å, Brene' S, Petterson R, Kvist S, Brownstein M, Hyman SE, Munke L, Goodman HM, Joh TH, Goldstein M, Hökfelt T (1987) Localization of mRNA for phenylethanolamine N-methyl transferase (PNMT) using in situ hybridization. Acta Physiol Scand 131:631–632

    Google Scholar 

  • Schalling M, Dagerlind A, Brene' S, Hallman H, Djurfeldt M, Persson H, Terenius L, Goldstein M, Schlesinger D, Hökfelt T (1988) Coexistence and gene expression of phenylethanolamine N-methyltransferase, tyrosine hydroxylase, and neuropeptide tyrosine in the rat and bovine adrenal gland: effects of reserpine. Proc Soc Natl Acad Sci USA 85:8306–8310

    Google Scholar 

  • Scheuermann DW, Timmermans DW, 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

    Google Scholar 

  • Seroogy K, Schalling M, Brene' S, Dagerlind Å, Chai S-Y, Hökfelt T, Persson H, Brownstein M, Dixon J, Filer D, Schlesinger D, Goldstein M (1989) Cholecystokinin and tyrosine hydroxylase messenger RNAs in neurons of rat mesencephalon: peptide/monoamine coexistence studies using in situ hybridization combined with immunocytochemistry. Exp Brain Res 74:149–162

    Google Scholar 

  • Tjen-A-Looi S, Keith IM, Lippton H (1991) CGRP, SOM-14, SOM-28 and their antagonists modulate hypoxic pulmonary hypertension in rats (Abstract 6160). FASEB J 5:A1432

  • 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

    Google Scholar 

  • Wada C, Kameya T, Ono M, Miki Y, Yamaguchi K (1987) a-calcitonin gene-related peptide (a-CGRP) and alternative RNA processing events in calcitonin/a-CGRP gene expression of human and rat lung. Kitasato Med 17:389–39517

    Google Scholar 

  • Wada C, Hashimoto C, Kameya T, Yamaguchi K, Ono M (1988) Developmentally regulated expression of the calcitonin gene related peptide (CGRP) in rat lung endocrine cells. Virchows Arch [B] 55:217–223

    Google Scholar 

  • Wiesenfeld-Hallin Z, Hökfelt T, Lundberg J, Forssman WG, Reinecke M, Tschopp FA, Fischer JA (1984) Immunoreactive calcitonin gene-related peptide and substance P coexist in sensory neurons to the spinal cord and interact in spinal behavioral responses of the rat. Neurosci Lett 52:199–204

    Google Scholar 

  • Yamaguchi K, Abe K, Adachi I, Kimura S, Szuki M, Shimada A, Kodama T, Kameya T, Shimosato Y (1985) Peptide hormone production in primary lung tumors. Recent Res Cancer Res 99:107–116

    Google Scholar 

  • Zzyzik-Krzeska MF, Bayliss DA, Seroogy KB, Millhorn DE (1991) Gene expression for peptides in neurons of the petrosal and nodose ganglia in rat. Exp Brain Res 83:411–418

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive, 53706, Madison, WI, USA

    I. M. Keith

  2. Department of Biomedical Sciences, University of Tampere, PO Box 607, SF-33101, Tampere, Finland

    M. Pelto-Huikko

  3. Department of Histology and Neurobiology, Karolinska Institute, PO Box 60400, S-10401, Stockholm, Sweden

    M. Schalling & T. Hökfelt

Authors
  1. I. M. Keith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Pelto-Huikko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Schalling
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. Hökfelt
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Keith, I.M., Pelto-Huikko, M., Schalling, M. et al. Calcitonin gene-related peptide and its mRNA in pulmonary neuroendocrine cells and ganglia. Histochemistry 96, 311–315 (1991). https://doi.org/10.1007/BF00271351

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00271351

Keywords

Search

Navigation