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. 1990 Jul;100(3):614–618. doi: 10.1111/j.1476-5381.1990.tb15855.x

Pharmacological evaluation of a guinea-pig tracheal epithelium-derived inhibitory factor (EpDIF).

L B Fernandes 1, R G Goldie 1
PMCID: PMC1917798  PMID: 2390683

Abstract

1. An epithelium-derived inhibitory factor (EpDIF) released by guinea-pig tracheal epithelium was evaluated in a co-axial bioassay system consisting of an epithelium-intact guinea-pig tracheal tube surrounding endothelium-denuded rat aortic strip. 2. Histamine and several muscarinic agonists induced concentration-dependent relaxation of phenylephrine-contracted rat aorta via the release of EpDIF. However, several other agonists did not induce the release of EpDIF from guinea-pig trachea. These included the nicotinic cholinoceptor agonists nicotine (25 microM), 1,1-dimethyl-4-phenylpiperazinium (DMPP) (25 microM), calcium ionophore A23187 (0.5 microM), bradykinin (0.05-0.5 microM), substance P (5 microM), platelet activating factor (PAF, 1-100 nM), the leukotrienes (LT) LTC4, LTD4 and LTE4 (0.1-10 nM) as well as hyperosmotic stimuli. 3. Prostaglandin E2 (PGE2) induced concentration-dependent contraction of endothelium-denuded rat aortic preparations, indicating that this prostanoid could not be EpDIF. Furthermore, relaxation to histamine and methacholine, mediated via EpDIF, was not significantly altered in the presence of phenidone (50 microM) the cyclo-oxygenase/lipoxygenase inhibitor with radical scavenging properties or the cytochrome P-450 inhibitors metyrapone (1 mM) and SKF 525A (25 microM). This suggests that EpDIF is neither a prostanoid nor a cytochrome P-450 metabolite of arachidonic acid. 4. The soluble guanylate cyclase inhibitor, methylene blue (50 microM), caused small but significant increases in the potencies of both histamine and methacholine in co-axial assemblies, indicating that EpDIF did not activate this enzyme and therefore was not NO or a related substance. The beta-adrenoceptor antagonist, (-)-propranolol (1 microM), and the PAF-receptor antagonist, WEB 2086 (50 microM), also failed to alter significantly EpDIF-modulated relaxations.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Aizawa H., Miyazaki N., Shigematsu N., Tomooka M. A possible role of airway epithelium in modulating hyperresponsiveness. Br J Pharmacol. 1988 Jan;93(1):139–145. doi: 10.1111/j.1476-5381.1988.tb11414.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnes P. J., Cuss F. M., Palmer J. B. The effect of airway epithelium on smooth muscle contractility in bovine trachea. Br J Pharmacol. 1985 Nov;86(3):685–691. doi: 10.1111/j.1476-5381.1985.tb08946.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barnett K., Jacoby D. B., Nadel J. A., Lazarus S. C. The effects of epithelial cell supernatant on contractions of isolated canine tracheal smooth muscle. Am Rev Respir Dis. 1988 Oct;138(4):780–783. doi: 10.1164/ajrccm/138.4.780. [DOI] [PubMed] [Google Scholar]
  4. Boushey H. A., Holtzman M. J., Sheller J. R., Nadel J. A. Bronchial hyperreactivity. Am Rev Respir Dis. 1980 Feb;121(2):389–413. doi: 10.1164/arrd.1980.121.2.389. [DOI] [PubMed] [Google Scholar]
  5. CHO A. K., HASLETT W. L., JENDEN D. J. The peripheral actions of oxotremorine, a metabolite of tremorine. J Pharmacol Exp Ther. 1962 Nov;138:249–257. [PubMed] [Google Scholar]
  6. Fernandes L. B., Paterson J. W., Goldie R. G. Co-axial bioassay of a smooth muscle relaxant factor released from guinea-pig tracheal epithelium. Br J Pharmacol. 1989 Jan;96(1):117–124. doi: 10.1111/j.1476-5381.1989.tb11791.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fine J. M., Gordon T., Sheppard D. Epithelium removal alters responsiveness of guinea pig trachea to substance P. J Appl Physiol (1985) 1989 Jan;66(1):232–237. doi: 10.1152/jappl.1989.66.1.232. [DOI] [PubMed] [Google Scholar]
  8. Flavahan N. A., Aarhus L. L., Rimele T. J., Vanhoutte P. M. Respiratory epithelium inhibits bronchial smooth muscle tone. J Appl Physiol (1985) 1985 Mar;58(3):834–838. doi: 10.1152/jappl.1985.58.3.834. [DOI] [PubMed] [Google Scholar]
  9. Frossard N., Muller F. Epithelial modulation of tracheal smooth muscle response to antigenic stimulation. J Appl Physiol (1985) 1986 Oct;61(4):1449–1456. doi: 10.1152/jappl.1986.61.4.1449. [DOI] [PubMed] [Google Scholar]
  10. Förstermann U., Alheid U., Frölich J. C., Mülsch A. Mechanisms of action of lipoxygenase and cytochrome P-450-mono-oxygenase inhibitors in blocking endothelium-dependent vasodilatation. Br J Pharmacol. 1988 Mar;93(3):569–578. doi: 10.1111/j.1476-5381.1988.tb10312.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gloge H., Lüllmann H., Mutschler E. The action of tertiary and quaternary arecaidine and dihydroarecaidine esters on the guinea pig isolated ileum. Br J Pharmacol Chemother. 1966 May;27(1):185–195. doi: 10.1111/j.1476-5381.1966.tb01654.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goldie R. G., Papadimitriou J. M., Paterson J. W., Rigby P. J., Self H. M., Spina D. Influence of the epithelium on responsiveness of guinea-pig isolated trachea to contractile and relaxant agonists. Br J Pharmacol. 1986 Jan;87(1):5–14. doi: 10.1111/j.1476-5381.1986.tb10150.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Güc M. O., Ilhan M., Kayaalp S. O. The rat anococcygeus muscle is a convenient bioassay organ for the airway epithelium-derived relaxant factor. Eur J Pharmacol. 1988 Apr 13;148(3):405–409. doi: 10.1016/0014-2999(88)90119-7. [DOI] [PubMed] [Google Scholar]
  14. Hay D. W., Farmer S. G., Raeburn D., Muccitelli R. M., Wilson K. A., Fedan J. S. Differential effects of epithelium removal on the responsiveness of guinea-pig tracheal smooth muscle to bronchoconstrictors. Br J Pharmacol. 1987 Oct;92(2):381–388. doi: 10.1111/j.1476-5381.1987.tb11334.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hisayama T., Takayanagi I., Nakazato F., Hirano K. Epithelium selectively controls hypersensitization of the response of smooth muscle to leukotriene D4 by endogenous prostanoid(s) in guinea-pig trachea. Naunyn Schmiedebergs Arch Pharmacol. 1988 Mar;337(3):296–300. doi: 10.1007/BF00168842. [DOI] [PubMed] [Google Scholar]
  16. Ilhan M., Sahin I. Tracheal epithelium releases a vascular smooth muscle relaxant factor: demonstration by bioassay. Eur J Pharmacol. 1986 Nov 19;131(2-3):293–296. doi: 10.1016/0014-2999(86)90586-8. [DOI] [PubMed] [Google Scholar]
  17. Jacoby D. B., Ueki I. F., Widdicombe J. H., Loegering D. A., Gleich G. J., Nadel J. A. Effect of human eosinophil major basic protein on ion transport in dog tracheal epithelium. Am Rev Respir Dis. 1988 Jan;137(1):13–16. doi: 10.1164/ajrccm/137.1.13. [DOI] [PubMed] [Google Scholar]
  18. Jancar S., Schulz R., Krueger C., Cook D. A. Mechanisms of arachidonic acid-induced contractions of canine cerebral arteries. Eur J Pharmacol. 1987 Apr 29;136(3):345–352. doi: 10.1016/0014-2999(87)90307-4. [DOI] [PubMed] [Google Scholar]
  19. Jeffery P. K., Wardlaw A. J., Nelson F. C., Collins J. V., Kay A. B. Bronchial biopsies in asthma. An ultrastructural, quantitative study and correlation with hyperreactivity. Am Rev Respir Dis. 1989 Dec;140(6):1745–1753. doi: 10.1164/ajrccm/140.6.1745. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Lundblad K. A., Persson C. G. The epithelium and the pharmacology of guinea-pig tracheal tone in vitro. Br J Pharmacol. 1988 Apr;93(4):909–917. doi: 10.1111/j.1476-5381.1988.tb11479.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Martin W., Villani G. M., Jothianandan D., Furchgott R. F. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta. J Pharmacol Exp Ther. 1985 Mar;232(3):708–716. [PubMed] [Google Scholar]
  23. Raeburn D., Hay D. W., Farmer S. G., Fedan J. S. Epithelium removal increases the reactivity of human isolated tracheal muscle to methacholine and reduces the effect of verapamil. Eur J Pharmacol. 1986 Apr 29;123(3):451–453. doi: 10.1016/0014-2999(86)90722-3. [DOI] [PubMed] [Google Scholar]
  24. Raeburn D., Sequeira D. J., Backes W. L. Possible involvement of cytochrome P-450 in the epithelium-modulated response to methacholine in guinea pig trachea. Biochem Pharmacol. 1988 Feb 15;37(4):573–576. doi: 10.1016/0006-2952(88)90127-x. [DOI] [PubMed] [Google Scholar]
  25. Tschirhart E., Frossard N., Bertrand C., Landry Y. Arachidonic acid metabolites and airway epithelium-dependent relaxant factor. J Pharmacol Exp Ther. 1987 Oct;243(1):310–316. [PubMed] [Google Scholar]
  26. Tschirhart E., Landry Y. Airway epithelium releases a relaxant factor: demonstration with substance P. Eur J Pharmacol. 1986 Dec 2;132(1):103–104. doi: 10.1016/0014-2999(86)90020-8. [DOI] [PubMed] [Google Scholar]
  27. Vanhoutte P. M. Epithelium-derived relaxing factor(s) and bronchial reactivity. Am Rev Respir Dis. 1988 Dec;138(6 Pt 2):S24–S30. doi: 10.1164/ajrccm/138.6_Pt_2.S24. [DOI] [PubMed] [Google Scholar]

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