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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1996 Nov 15;98(10):2284–2291. doi: 10.1172/JCI119039

Induction of tachykinin gene and peptide expression in guinea pig nodose primary afferent neurons by allergic airway inflammation.

A Fischer 1, G P McGregor 1, A Saria 1, B Philippin 1, W Kummer 1
PMCID: PMC507678  PMID: 8941645

Abstract

Substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP) have potent proinflammatory effects in the airways. They are released from sensory nerve endings originating in jugular and dorsal root ganglia. However, the major sensory supply to the airways originates from the nodose ganglion. In this study, we evaluated changes in neuropeptide biosynthesis in the sensory airway innervation of ovalbumin-sensitized and -challenged guinea pigs at the mRNA and peptide level. In the airways, a three- to fourfold increase of SP, NKA, and CGRP, was seen 24 h following allergen challenge. Whereas no evidence of local tachykinin biosynthesis was found 12 h after challenge, increased levels of preprotachykinin (PPT)-A mRNA (encoding SP and NKA) were found in nodose ganglia. Quantitative in situ hybridization indicated that this increase could be accounted for by de novo induction of PPT-A mRNA in nodose ganglion neurons. Quantitative immunohistochemistry showed that 24 h after challenge, the number of tachykinin-immunoreactive nodose ganglion neurons had increased by 25%. Their projection to the airways was shown. Changes in other sensory ganglia innervating the airways were not evident. These findings suggest that an induction of sensory neuropeptides in nodose ganglion neurons is crucially involved in the increase of airway hyperreactivity in the late response to allergen challenge.

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Selected References

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  1. Adcock I. M., Peters M., Gelder C., Shirasaki H., Brown C. R., Barnes P. J. Increased tachykinin receptor gene expression in asthmatic lung and its modulation by steroids. J Mol Endocrinol. 1993 Aug;11(1):1–7. doi: 10.1677/jme.0.0110001. [DOI] [PubMed] [Google Scholar]
  2. Barnes P. J., Baraniuk J. N., Belvisi M. G. Neuropeptides in the respiratory tract. Part I. Am Rev Respir Dis. 1991 Nov;144(5):1187–1198. doi: 10.1164/ajrccm/144.5.1187. [DOI] [PubMed] [Google Scholar]
  3. Barnes P. J., Baraniuk J. N., Belvisi M. G. Neuropeptides in the respiratory tract. Part II. Am Rev Respir Dis. 1991 Dec;144(6):1391–1399. doi: 10.1164/ajrccm/144.6.1391. [DOI] [PubMed] [Google Scholar]
  4. Barnes P. J. Neurogenic inflammation in airways and its modulation. Arch Int Pharmacodyn Ther. 1990 Jan-Feb;303:67–82. [PubMed] [Google Scholar]
  5. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  6. Donaldson L. F., Harmar A. J., McQueen D. S., Seckl J. R. Increased expression of preprotachykinin, calcitonin gene-related peptide, but not vasoactive intestinal peptide messenger RNA in dorsal root ganglia during the development of adjuvant monoarthritis in the rat. Brain Res Mol Brain Res. 1992 Nov;16(1-2):143–149. doi: 10.1016/0169-328x(92)90204-o. [DOI] [PubMed] [Google Scholar]
  7. Donnerer J., Schuligoi R., Stein C., Amann R. Upregulation, release and axonal transport of substance P and calcitonin gene-related peptide in adjuvant inflammation and regulatory function of nerve growth factor. Regul Pept. 1993 Jul 2;46(1-2):150–154. [PubMed] [Google Scholar]
  8. Donnerer J., Schuligoi R., Stein C. Increased content and transport of substance P and calcitonin gene-related peptide in sensory nerves innervating inflamed tissue: evidence for a regulatory function of nerve growth factor in vivo. Neuroscience. 1992 Aug;49(3):693–698. doi: 10.1016/0306-4522(92)90237-v. [DOI] [PubMed] [Google Scholar]
  9. Escher E., Couture R., Poulos C., Pinas N., Mizrahi J., Theodoropoulos D., Regoli D. Structure-activity studies on the C-terminal amide of substance P. J Med Chem. 1982 Nov;25(11):1317–1321. doi: 10.1021/jm00353a009. [DOI] [PubMed] [Google Scholar]
  10. Frossard N., Advenier C. Tachykinin receptors and the airways. Life Sci. 1991;49(26):1941–1953. doi: 10.1016/0024-3205(91)90636-p. [DOI] [PubMed] [Google Scholar]
  11. Helke C. J., Rabchevsky A. Axotomy alters putative neurotransmitters in visceral sensory neurons of the nodose and petrosal ganglia. Brain Res. 1991 Jun 14;551(1-2):44–51. doi: 10.1016/0006-8993(91)90911-e. [DOI] [PubMed] [Google Scholar]
  12. Hsiue T. R., Garland A., Ray D. W., Hershenson M. B., Leff A. R., Solway J. Endogenous sensory neuropeptide release enhances nonspecific airway responsiveness in guinea pigs. Am Rev Respir Dis. 1992 Jul;146(1):148–153. doi: 10.1164/ajrccm/146.1.148. [DOI] [PubMed] [Google Scholar]
  13. Huang F. L., Zhuo H., Sinclair C., Goldstein M. E., McCabe J. T., Helke C. J. Peripheral deafferentation alters calcitonin gene-related peptide mRNA expression in visceral sensory neurons of the nodose and petrosal ganglia. Brain Res Mol Brain Res. 1994 Mar;22(1-4):290–298. doi: 10.1016/0169-328x(94)90057-4. [DOI] [PubMed] [Google Scholar]
  14. Humpel C., Neudorfer C., Philipp W., Steiner H. J., Haring C., Schmid K. W., Schwitzer J., Saria A. Effects of bright artificial light on monoamines and neuropeptides in eight different brain regions compared in a pigmented and nonpigmented rat strain. J Neurosci Res. 1992 Aug;32(4):605–612. doi: 10.1002/jnr.490320416. [DOI] [PubMed] [Google Scholar]
  15. Hutson P. A., Church M. K., Clay T. P., Miller P., Holgate S. T. Early and late-phase bronchoconstriction after allergen challenge of nonanesthetized guinea pigs. I. The association of disordered airway physiology to leukocyte infiltration. Am Rev Respir Dis. 1988 Mar;137(3):548–557. doi: 10.1164/ajrccm/137.3.548. [DOI] [PubMed] [Google Scholar]
  16. Hökfelt T., Zhang X., Wiesenfeld-Hallin Z. Messenger plasticity in primary sensory neurons following axotomy and its functional implications. Trends Neurosci. 1994 Jan;17(1):22–30. doi: 10.1016/0166-2236(94)90031-0. [DOI] [PubMed] [Google Scholar]
  17. Krause J. E., Chirgwin J. M., Carter M. S., Xu Z. S., Hershey A. D. Three rat preprotachykinin mRNAs encode the neuropeptides substance P and neurokinin A. Proc Natl Acad Sci U S A. 1987 Feb;84(3):881–885. doi: 10.1073/pnas.84.3.881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kummer W., Bachmann S., Neuhuber W. L., Hänze J., Lang R. E. Tyrosine-hydroxylase-containing vagal afferent neurons in the rat nodose ganglion are independent from neuropeptide-Y-containing populations and project to esophagus and stomach. Cell Tissue Res. 1993 Jan;271(1):135–144. doi: 10.1007/BF00297551. [DOI] [PubMed] [Google Scholar]
  19. Kummer W., Fischer A., Kurkowski R., Heym C. The sensory and sympathetic innervation of guinea-pig lung and trachea as studied by retrograde neuronal tracing and double-labelling immunohistochemistry. Neuroscience. 1992 Aug;49(3):715–737. doi: 10.1016/0306-4522(92)90239-x. [DOI] [PubMed] [Google Scholar]
  20. Kuo H. P., Rohde J. A., Tokuyama K., Barnes P. J., Rogers D. F. Capsaicin and sensory neuropeptide stimulation of goblet cell secretion in guinea-pig trachea. J Physiol. 1990 Dec;431:629–641. doi: 10.1113/jphysiol.1990.sp018351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Laitinen L. A., Heino M., Laitinen A., Kava T., Haahtela T. Damage of the airway epithelium and bronchial reactivity in patients with asthma. Am Rev Respir Dis. 1985 Apr;131(4):599–606. doi: 10.1164/arrd.1985.131.4.599. [DOI] [PubMed] [Google Scholar]
  22. Lei Y. H., Barnes P. J., Rogers D. F. Inhibition of neurogenic plasma exudation in guinea-pig airways by CP-96,345, a new non-peptide NK1 receptor antagonist. Br J Pharmacol. 1992 Feb;105(2):261–262. doi: 10.1111/j.1476-5381.1992.tb14243.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Levine J. D., Fields H. L., Basbaum A. I. Peptides and the primary afferent nociceptor. J Neurosci. 1993 Jun;13(6):2273–2286. doi: 10.1523/JNEUROSCI.13-06-02273.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lou Y. P., Lee L. Y., Satoh H., Lundberg J. M. Postjunctional inhibitory effect of the NK2 receptor antagonist, SR 48968, on sensory NANC bronchoconstriction in the guinea-pig. Br J Pharmacol. 1993 Jul;109(3):765–773. doi: 10.1111/j.1476-5381.1993.tb13640.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lundberg J. M., Hökfelt T., Martling C. R., Saria A., Cuello C. Substance P-immunoreactive sensory nerves in the lower respiratory tract of various mammals including man. Cell Tissue Res. 1984;235(2):251–261. doi: 10.1007/BF00217848. [DOI] [PubMed] [Google Scholar]
  26. Martling C. R., Saria A., Fischer J. A., Hökfelt T., Lundberg J. M. Calcitonin gene-related peptide and the lung: neuronal coexistence with substance P, release by capsaicin and vasodilatory effect. Regul Pept. 1988 Feb;20(2):125–139. doi: 10.1016/0167-0115(88)90046-8. [DOI] [PubMed] [Google Scholar]
  27. McGregor G. P., Hartel R., Haberberger R., Kummer W., Voigt K. Preprotachykinin-A gene expression occurs transiently in the developing rat endocrine pancreas and can be regulated in RINm5F cells. Endocrinology. 1995 Jun;136(6):2538–2546. doi: 10.1210/endo.136.6.7538464. [DOI] [PubMed] [Google Scholar]
  28. Mundel P., Bachmann S., Bader M., Fischer A., Kummer W., Mayer B., Kriz W. Expression of nitric oxide synthase in kidney macula densa cells. Kidney Int. 1992 Oct;42(4):1017–1019. doi: 10.1038/ki.1992.382. [DOI] [PubMed] [Google Scholar]
  29. Nadel J. A. Neurogenic inflammation in airways and its modulation by peptidases. Ann N Y Acad Sci. 1992;664:408–414. doi: 10.1111/j.1749-6632.1992.tb39779.x. [DOI] [PubMed] [Google Scholar]
  30. Nieber K., Baumgarten C. R., Rathsack R., Furkert J., Oehme P., Kunkel G. Substance P and beta-endorphin-like immunoreactivity in lavage fluids of subjects with and without allergic asthma. J Allergy Clin Immunol. 1992 Oct;90(4 Pt 1):646–652. doi: 10.1016/0091-6749(92)90138-r. [DOI] [PubMed] [Google Scholar]
  31. Noguchi K., Morita Y., Kiyama H., Ono K., Tohyama M. A noxious stimulus induces the preprotachykinin-A gene expression in the rat dorsal root ganglion: a quantitative study using in situ hybridization histochemistry. Brain Res. 1988 Aug;464(1):31–35. doi: 10.1016/0169-328x(88)90015-0. [DOI] [PubMed] [Google Scholar]
  32. Noguchi K., Senba E., Morita Y., Sato M., Tohyama M. Prepro-VIP and preprotachykinin mRNAs in the rat dorsal root ganglion cells following peripheral axotomy. Brain Res Mol Brain Res. 1989 Dec;6(4):327–330. doi: 10.1016/0169-328x(89)90077-6. [DOI] [PubMed] [Google Scholar]
  33. Pernow B. Role of tachykinins in neurogenic inflammation. J Immunol. 1985 Aug;135(2 Suppl):812s–815s. [PubMed] [Google Scholar]
  34. Sanjar S., Aoki S., Kristersson A., Smith D., Morley J. Antigen challenge induces pulmonary airway eosinophil accumulation and airway hyperreactivity in sensitized guinea-pigs: the effect of anti-asthma drugs. Br J Pharmacol. 1990 Apr;99(4):679–686. doi: 10.1111/j.1476-5381.1990.tb12989.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Saria A., Martling C. R., Dalsgaard C. J., Lundberg J. M. Evidence for substance P-immunoreactive spinal afferents that mediate bronchoconstriction. Acta Physiol Scand. 1985 Nov;125(3):407–414. doi: 10.1111/j.1748-1716.1985.tb07736.x. [DOI] [PubMed] [Google Scholar]
  36. Saria A., Martling C. R., Yan Z., Theodorsson-Norheim E., Gamse R., Lundberg J. M. Release of multiple tachykinins from capsaicin-sensitive sensory nerves in the lung by bradykinin, histamine, dimethylphenyl piperazinium, and vagal nerve stimulation. Am Rev Respir Dis. 1988 Jun;137(6):1330–1335. doi: 10.1164/ajrccm/137.6.1330. [DOI] [PubMed] [Google Scholar]
  37. Solway J., Leff A. R. Sensory neuropeptides and airway function. J Appl Physiol (1985) 1991 Dec;71(6):2077–2087. doi: 10.1152/jappl.1991.71.6.2077. [DOI] [PubMed] [Google Scholar]
  38. Springall D. R., Cadieux A., Oliveira H., Su H., Royston D., Polak J. M. Retrograde tracing shows that CGRP-immunoreactive nerves of rat trachea and lung originate from vagal and dorsal root ganglia. J Auton Nerv Syst. 1987 Aug;20(2):155–166. doi: 10.1016/0165-1838(87)90113-5. [DOI] [PubMed] [Google Scholar]
  39. Yoshihara S. [Immunoreactive substance P levels in respiratory tract tissues of normal and airway-allergic guinea pigs]. Arerugi. 1988 Dec;37(12):1161–1168. [PubMed] [Google Scholar]

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