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. 1990 Apr;85(4):998–1005. doi: 10.1172/JCI114577

Gastrin-releasing peptide in human nasal mucosa.

J N Baraniuk 1, J D Lundgren 1, J Goff 1, D Peden 1, M Merida 1, J Shelhamer 1, M Kaliner 1
PMCID: PMC296528  PMID: 2318984

Abstract

Gastrin-releasing peptide (GRP), the 27 amino acid mammalian form of bombesin, was studied in human inferior turbinate nasal mucosa. The GRP content of the mucosa measured by radioimmunoassay was 0.60 +/- 0.25 pmol/g tissue (n = 9 patients; mean +/- SEM). GRP-immunoreactive nerves detected by the immunogold method of indirect immunohistochemistry were found predominantly in small muscular arteries, arterioles, venous sinusoids, and between submucosal gland acini. 125I-GRP binding sites determined by autoradiography were exclusively and specifically localized to nasal epithelium and submucosal glands. There was no binding to vessels. The effects of GRP on submucosal gland product release were studied in short-term explant culture. GRP (10 microM) significantly stimulated the release of the serous cell-specific product lactoferrin, and [3H]glucosamine-labeled glycoconjugates which are products of epithelial goblet cells and submucosal gland cells. These observations indicate that GRP released from nerve fibers probably acts on glandular GRP receptors to induce glycoconjugate release from submucosal glands and epithelium and lactoferrin release from serous cells, but that GRP would probably not affect vascular permeability.

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Selected References

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  1. Aguayo S. M., Kane M. A., King T. E., Jr, Schwarz M. I., Grauer L., Miller Y. E. Increased levels of bombesin-like peptides in the lower respiratory tract of asymptomatic cigarette smokers. J Clin Invest. 1989 Oct;84(4):1105–1113. doi: 10.1172/JCI114273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alexander R. W., Upp J. R., Jr, Poston G. J., Gupta V., Townsend C. M., Jr, Thompson J. C. Effects of bombesin on growth of human small cell lung carcinoma in vivo. Cancer Res. 1988 Mar 15;48(6):1439–1441. [PubMed] [Google Scholar]
  3. Barnes P. J. Asthma as an axon reflex. Lancet. 1986 Feb 1;1(8475):242–245. doi: 10.1016/s0140-6736(86)90777-4. [DOI] [PubMed] [Google Scholar]
  4. Bork E., Hansen M., Urdal P., Paus E., Holst J. J., Schifter S., Fenger M., Engbaek F. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide. Eur J Cancer Clin Oncol. 1988 Jun;24(6):1033–1038. doi: 10.1016/0277-5379(88)90154-x. [DOI] [PubMed] [Google Scholar]
  5. Brain S. D., Williams T. J. Substance P regulates the vasodilator activity of calcitonin gene-related peptide. Nature. 1988 Sep 1;335(6185):73–75. doi: 10.1038/335073a0. [DOI] [PubMed] [Google Scholar]
  6. Cuttitta F., Carney D. N., Mulshine J., Moody T. W., Fedorko J., Fischler A., Minna J. D. Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. 1985 Aug 29-Sep 4Nature. 316(6031):823–826. doi: 10.1038/316823a0. [DOI] [PubMed] [Google Scholar]
  7. Cuttitta F., Fedorko J., Gu J. A., Lebacq-Verheyden A. M., Linnoila R. I., Battey J. F. Gastrin-releasing peptide gene-associated peptides are expressed in normal human fetal lung and small cell lung cancer: a novel peptide family found in man. J Clin Endocrinol Metab. 1988 Sep;67(3):576–583. doi: 10.1210/jcem-67-3-576. [DOI] [PubMed] [Google Scholar]
  8. Damgé C., Hajri A., Lhoste E., Aprahamian M. Comparative effect of chronic bombesin, gastrin-releasing peptide and caerulein on the rat pancreas. Regul Pept. 1988 Feb;20(2):141–150. doi: 10.1016/0167-0115(88)90047-x. [DOI] [PubMed] [Google Scholar]
  9. Davis B., Roberts A. M., Coleridge H. M., Coleridge J. C. Reflex tracheal gland secretion evoked by stimulation of bronchial C-fibers in dogs. J Appl Physiol Respir Environ Exerc Physiol. 1982 Oct;53(4):985–991. doi: 10.1152/jappl.1982.53.4.985. [DOI] [PubMed] [Google Scholar]
  10. Geppetti P., Maggi C. A., Perretti F., Frilli S., Manzini S. Simultaneous release by bradykinin of substance P- and calcitonin gene-related peptide immunoreactivities from capsaicin-sensitive structures in guinea-pig heart. Br J Pharmacol. 1988 Jun;94(2):288–290. doi: 10.1111/j.1476-5381.1988.tb11528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Haraguchi Y., Sakamoto A., Yoshida T., Tanaka K. Plasma GRP-like immunoreactivity in healthy and diseased subjects. Gastroenterol Jpn. 1988 Jun;23(3):247–250. doi: 10.1007/BF02779466. [DOI] [PubMed] [Google Scholar]
  12. Helen P., Panula P., Yang H. Y., Hervonen A., Rapoport S. I. Location of substance P-, bombesin-gastrin-releasing peptide, [Met5]enkephalin- and [Met5]enkephalin-Arg6-Phe7-like immunoreactivities in adult human sympathetic ganglia. Neuroscience. 1984 Jul;12(3):907–916. doi: 10.1016/0306-4522(84)90178-7. [DOI] [PubMed] [Google Scholar]
  13. Holst J. J., Knuhtsen S., Orskov C., Skak-Nielsen T., Poulsen S. S., Jensen S. L., Nielsen O. V. GRP nerves in pig antrum: role of GRP in vagal control of gastrin secretion. Am J Physiol. 1987 Nov;253(5 Pt 1):G643–G649. doi: 10.1152/ajpgi.1987.253.5.G643. [DOI] [PubMed] [Google Scholar]
  14. Holzer P. Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience. 1988 Mar;24(3):739–768. doi: 10.1016/0306-4522(88)90064-4. [DOI] [PubMed] [Google Scholar]
  15. Hua X. Y. Tachykinins and calcitonin gene-related peptide in relation to peripheral functions of capsaicin-sensitive sensory neurons. Acta Physiol Scand Suppl. 1986;551:1–45. [PubMed] [Google Scholar]
  16. Kentroti S., Dees W. L., McCann S. M. Evidence for a physiological role of hypothalamic gastrin-releasing peptide to suppress growth hormone and prolactin release in the rat. Proc Natl Acad Sci U S A. 1988 Feb;85(3):953–957. doi: 10.1073/pnas.85.3.953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Khalil Z., Andrews P. V., Helme R. D. VIP modulates substance P-induced plasma extravasation in vivo. Eur J Pharmacol. 1988 Jul 7;151(2):281–287. doi: 10.1016/0014-2999(88)90809-6. [DOI] [PubMed] [Google Scholar]
  18. Kris R. M., Hazan R., Villines J., Moody T. W., Schlessinger J. Identification of the bombesin receptor on murine and human cells by cross-linking experiments. J Biol Chem. 1987 Aug 15;262(23):11215–11220. [PubMed] [Google Scholar]
  19. Lenz H. J. CNS regulation of gastric and autonomic functions in dogs by gastrin-releasing peptide. Am J Physiol. 1988 Sep;255(3 Pt 1):G298–G303. doi: 10.1152/ajpgi.1988.255.3.G298. [DOI] [PubMed] [Google Scholar]
  20. Login G. R., Schnitt S. J., Dvorak A. M. Rapid microwave fixation of human tissues for light microscopic immunoperoxidase identification of diagnostically useful antigens. Lab Invest. 1987 Nov;57(5):585–591. [PubMed] [Google Scholar]
  21. Lundblad L. Protective reflexes and vascular effects in the nasal mucosa elicited by activation of capsaicin-sensitive substance P-immunoreactive trigeminal neurons. Acta Physiol Scand Suppl. 1984;529:1–42. [PubMed] [Google Scholar]
  22. Lundgren J. D., Wiedermann C. J., Logun C., Plutchok J., Kaliner M., Shelhamer J. H. Substance P receptor-mediated secretion of respiratory glycoconjugate from feline airways in vitro. Exp Lung Res. 1989;15(1):17–29. doi: 10.3109/01902148909069606. [DOI] [PubMed] [Google Scholar]
  23. Marom Z., Shelhamer J., Kaliner M. Nasal mucus secretion. Ear Nose Throat J. 1984 Feb;63(2):36-7, 41-2, 44. [PubMed] [Google Scholar]
  24. McKillop J. M., Foy W. L., Johnston C. F., Shaw C., Murphy R. F., Buchanan K. D. Gastrin-releasing peptide (GRP) immunoreactivity in the rat retina: a radioimmunoassay, immunohistochemical and chromatographic study. Brain Res. 1988 May 3;447(2):239–245. doi: 10.1016/0006-8993(88)91125-0. [DOI] [PubMed] [Google Scholar]
  25. Moran T. H., Moody T. W., Hostetler A. M., Robinson P. H., Goldrich M., McHugh P. R. Distribution of bombesin binding sites in the rat gastrointestinal tract. Peptides. 1988 May-Jun;9(3):643–649. doi: 10.1016/0196-9781(88)90177-5. [DOI] [PubMed] [Google Scholar]
  26. Panula P., Hadjiconstantinou M., Yang H. Y., Costa E. Immunohistochemical localization of bombesin/gastrin-releasing peptide and substance P in primary sensory neurons. J Neurosci. 1983 Oct;3(10):2021–2029. doi: 10.1523/JNEUROSCI.03-10-02021.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Panula P. Histochemistry and function of bombesin-like peptides. Med Biol. 1986;64(4):177–192. [PubMed] [Google Scholar]
  28. Polak J. M., Bloom S. R. Occurrence and distribution of regulatory peptides in the respiratory tract. Recent Results Cancer Res. 1985;99:1–16. doi: 10.1007/978-3-642-82533-0_1. [DOI] [PubMed] [Google Scholar]
  29. Raphael G. D., Druce H. M., Baraniuk J. N., Kaliner M. A. Pathophysiology of rhinitis. 1. Assessment of the sources of protein in methacholine-induced nasal secretions. Am Rev Respir Dis. 1988 Aug;138(2):413–420. doi: 10.1164/ajrccm/138.2.413. [DOI] [PubMed] [Google Scholar]
  30. Raphael G. D., Druce H. M., Baraniuk J. N., Kaliner M. A. Pathophysiology of rhinitis. 1. Assessment of the sources of protein in methacholine-induced nasal secretions. Am Rev Respir Dis. 1988 Aug;138(2):413–420. doi: 10.1164/ajrccm/138.2.413. [DOI] [PubMed] [Google Scholar]
  31. Raphael G., Raphael M. H., Kaliner M. Gustatory rhinitis: a syndrome of food-induced rhinorrhea. J Allergy Clin Immunol. 1989 Jan;83(1):110–115. doi: 10.1016/0091-6749(89)90484-3. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Shelhamer J. H., Marom Z., Kaliner M. Immunologic and neuropharmacologic stimulation of mucous glycoprotein release from human airways in vitro. J Clin Invest. 1980 Dec;66(6):1400–1408. doi: 10.1172/JCI109993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Shinozaki H., Funakoshi A. Evidence for the direct action of gastrin-releasing peptide (GRP) on amylase secretion from rat pancreatic acini: an assessment using a perifusion system. Jpn J Physiol. 1988;38(3):299–307. doi: 10.2170/jjphysiol.38.299. [DOI] [PubMed] [Google Scholar]
  35. Spindel E. R., Sunday M. E., Hofler H., Wolfe H. J., Habener J. F., Chin W. W. Transient elevation of messenger RNA encoding gastrin-releasing peptide, a putative pulmonary growth factor in human fetal lung. J Clin Invest. 1987 Oct;80(4):1172–1179. doi: 10.1172/JCI113176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sunday M. E., Kaplan L. M., Motoyama E., Chin W. W., Spindel E. R. Gastrin-releasing peptide (mammalian bombesin) gene expression in health and disease. Lab Invest. 1988 Jul;59(1):5–24. [PubMed] [Google Scholar]
  37. Tabassian A. R., Nylen E. S., Linnoila R. I., Snider R. H., Cassidy M. M., Becker K. L. Stimulation of hamster pulmonary neuroendocrine cells and associated peptides by repeated exposure to cigarette smoke. Am Rev Respir Dis. 1989 Aug;140(2):436–440. doi: 10.1164/ajrccm/140.2.436. [DOI] [PubMed] [Google Scholar]
  38. Uddman R., Sundler F. Innervation of the upper airways. Clin Chest Med. 1986 Jun;7(2):201–209. [PubMed] [Google Scholar]
  39. Walsh J. H. Peptides as regulators of gastric acid secretion. Annu Rev Physiol. 1988;50:41–63. doi: 10.1146/annurev.ph.50.030188.000353. [DOI] [PubMed] [Google Scholar]
  40. Willey J. C., Lechner J. F., Harris C. C. Bombesin and the C-terminal tetradecapeptide of gastrin-releasing peptide are growth factors for normal human bronchial epithelial cells. Exp Cell Res. 1984 Jul;153(1):245–248. doi: 10.1016/0014-4827(84)90466-x. [DOI] [PubMed] [Google Scholar]

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