Skip to main content
NCBI home page
Thorax logoLink to Thorax
. 1996 Dec;51(12):1199–1202. doi: 10.1136/thx.51.12.1199

Potentiation of the bronchoprotective effects of vasoactive intestinal peptide, isoprenaline, and theophylline against histamine challenge in anaesthetised guinea pigs by adrenomedullin.

H Kanazawa 1, T Kawaguchi 1, T Fujii 1, S Shoji 1, K Hirata 1, S Kudoh 1, N Kurihara 1, J Yoshikawa 1
PMCID: PMC472763  PMID: 8994515

Abstract

BACKGROUND: Adrenomedullin is a hypotensive peptide recently discovered in human phaeochromocytoma which has been found to inhibit bronchoconstriction induced by histamine and acetylcholine. This study was designed to determine the manner in which adrenomedullin and other bronchodilators interact in modulating airway function. METHODS: A study was undertaken to determine whether adrenomedullin potentiated the bronchoprotective effects of isoprenaline, vasoactive intestinal peptide (VIP), and theophylline against histamine-induced bronchoconstriction in anaesthetised guinea pigs in vivo. RESULTS: Adrenomedullin in a concentration of 10(-9) M significantly inhibited histamine-induced bronchoconstriction but in a concentration of 10(-10) M it did not exhibit the bronchoprotective effect against histamine. VIP (10(-9) M) did not affect histamine-induced bronchoconstriction but it markedly inhibited the bronchoprotective effect against histamine in the presence of adrenomedullin (10(-10) M). VIP (10(-6) M) significantly inhibited histamine-induced bronchoconstriction but this effect was short lived. Adrenomedullin in a concentration of 10(-10) M potentiated bronchoprotection induced by VIP (10(-6) M) and prolonged it. Isoprenaline (10(-8) M) also significantly inhibited histamine-induced bronchoconstriction and this effect was enhanced in the presence of adrenomedullin (10(-10) M). Similarly, adrenomedullin (10(-10) M) significantly potentiated theophylline-induced bronchoprotection, and a sub-bronchoprotective dose of theophylline (20 mg/kg i.p.) was effective in preventing histamine-induced bronchoconstriction in the presence of adrenomedullin (10(-10) M). CONCLUSIONS: This study shows that adrenomedullin potentiates the bronchoprotective effects of different classes of bronchodilators against histamine challenge in anaesthetised guinea pigs.

Full text

PDF
1199

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barnes P. J., Dixon C. M. The effect of inhaled vasoactive intestinal peptide on bronchial reactivity to histamine in humans. Am Rev Respir Dis. 1984 Aug;130(2):162–166. doi: 10.1164/arrd.1984.130.2.162. [DOI] [PubMed] [Google Scholar]
  2. Bundgaard A., Enehjelm S. D., Aggestrup S. Pretreatment of exercise-induced asthma with inhaled vasoactive intestinal peptide (VIP). Eur J Respir Dis Suppl. 1983;128(Pt 2):427–429. [PubMed] [Google Scholar]
  3. Dey R. D., Shannon W. A., Jr, Said S. I. Localization of VIP-immunoreactive nerves in airways and pulmonary vessels of dogs, cat, and human subjects. Cell Tissue Res. 1981;220(2):231–238. doi: 10.1007/BF00210505. [DOI] [PubMed] [Google Scholar]
  4. Diamond L., Szarek J. L., Gillespie M. N., Altiere R. J. In vivo bronchodilator activity of vasoactive intestinal peptide in the cat. Am Rev Respir Dis. 1983 Nov;128(5):827–832. doi: 10.1164/arrd.1983.128.5.827. [DOI] [PubMed] [Google Scholar]
  5. Dusser D. J., Umeno E., Graf P. D., Djokic T., Borson D. B., Nadel J. A. Airway neutral endopeptidase-like enzyme modulates tachykinin-induced bronchoconstriction in vivo. J Appl Physiol (1985) 1988 Dec;65(6):2585–2591. doi: 10.1152/jappl.1988.65.6.2585. [DOI] [PubMed] [Google Scholar]
  6. Eguchi S., Hirata Y., Kano H., Sato K., Watanabe Y., Watanabe T. X., Nakajima K., Sakakibara S., Marumo F. Specific receptors for adrenomedullin in cultured rat vascular smooth muscle cells. FEBS Lett. 1994 Mar 7;340(3):226–230. doi: 10.1016/0014-5793(94)80143-6. [DOI] [PubMed] [Google Scholar]
  7. Ishiyama Y., Kitamura K., Ichiki Y., Nakamura S., Kida O., Kangawa K., Eto T. Hemodynamic effects of a novel hypotensive peptide, human adrenomedullin, in rats. Eur J Pharmacol. 1993 Sep 14;241(2-3):271–273. doi: 10.1016/0014-2999(93)90214-3. [DOI] [PubMed] [Google Scholar]
  8. Kanazawa H., Kurihara N., Hirata K., Kudoh S., Kawaguchi T., Takeda T. Adrenomedullin, a newly discovered hypotensive peptide, is a potent bronchodilator. Biochem Biophys Res Commun. 1994 Nov 30;205(1):251–254. doi: 10.1006/bbrc.1994.2657. [DOI] [PubMed] [Google Scholar]
  9. Kitamura K., Kangawa K., Kawamoto M., Ichiki Y., Nakamura S., Matsuo H., Eto T. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun. 1993 Apr 30;192(2):553–560. doi: 10.1006/bbrc.1993.1451. [DOI] [PubMed] [Google Scholar]
  10. Kitamura K., Kangawa K., Kojima M., Ichiki Y., Matsuo H., Eto T. Complete amino acid sequence of porcine adrenomedullin and cloning of cDNA encoding its precursor. FEBS Lett. 1994 Feb 7;338(3):306–310. doi: 10.1016/0014-5793(94)80289-0. [DOI] [PubMed] [Google Scholar]
  11. Martinez A., Miller M. J., Unsworth E. J., Siegfried J. M., Cuttitta F. Expression of adrenomedullin in normal human lung and in pulmonary tumors. Endocrinology. 1995 Sep;136(9):4099–4105. doi: 10.1210/endo.136.9.7649118. [DOI] [PubMed] [Google Scholar]
  12. O'Donnell M., Garippa R. J., Rinaldi N., Selig W. M., Simko B., Renzetti L., Tannu S. A., Wasserman M. A., Welton A., Bolin D. R. Ro 25-1553: a novel, long-acting vasoactive intestinal peptide agonist. Part I: In vitro and in vivo bronchodilator studies. J Pharmacol Exp Ther. 1994 Sep;270(3):1282–1288. [PubMed] [Google Scholar]
  13. Palmer J. B., Cuss F. M., Barnes P. J. VIP and PHM and their role in nonadrenergic inhibitory responses in isolated human airways. J Appl Physiol (1985) 1986 Oct;61(4):1322–1328. doi: 10.1152/jappl.1986.61.4.1322. [DOI] [PubMed] [Google Scholar]
  14. Palmer J. B., Cuss F. M., Warren J. B., Blank M., Bloom S. R., Barnes P. J. Effect of infused vasoactive intestinal peptide on airway function in normal subjects. Thorax. 1986 Sep;41(9):663–666. doi: 10.1136/thx.41.9.663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Polak J. M., Bloom S. R. Regulatory peptides of the gastrointestinal and respiratory tracts. Arch Int Pharmacodyn Ther. 1986 Apr;280(2 Suppl):16–49. [PubMed] [Google Scholar]
  16. Santing R. E., Olymulder C. G., Van der Molen K., Meurs H., Zaagsma J. Phosphodiesterase inhibitors reduce bronchial hyperreactivity and airway inflammation in unrestrained guinea pigs. Eur J Pharmacol. 1995 Feb 24;275(1):75–82. doi: 10.1016/0014-2999(94)00749-w. [DOI] [PubMed] [Google Scholar]
  17. Torphy T. J., Burman M., Huang L. B., Tucker S. S. Inhibition of the low km cyclic AMP phosphodiesterase in intact canine trachealis by SK&F 94836: mechanical and biochemical responses. J Pharmacol Exp Ther. 1988 Sep;246(3):843–850. [PubMed] [Google Scholar]
  18. Torphy T. J., Undem B. J., Cieslinski L. B., Luttmann M. A., Reeves M. L., Hay D. W. Identification, characterization and functional role of phosphodiesterase isozymes in human airway smooth muscle. J Pharmacol Exp Ther. 1993 Jun;265(3):1213–1223. [PubMed] [Google Scholar]
  19. de Boer J., Philpott A. J., van Amsterdam R. G., Shahid M., Zaagsma J., Nicholson C. D. Human bronchial cyclic nucleotide phosphodiesterase isoenzymes: biochemical and pharmacological analysis using selective inhibitors. Br J Pharmacol. 1992 Aug;106(4):1028–1034. doi: 10.1111/j.1476-5381.1992.tb14451.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES