Abstract
1 The influence of the epithelium on contractions produced by the peptidoleukotrienes, 5-hydroxytryptamine (5-HT) and the thromboxane mimetic, U-44069, was examined in trachea from control and ovalbumin-sensitized guinea-pigs. 2 In control tissues removal of the epithelium produced an approximately 2 to 4 fold leftward shift in leukotriene C4 (LTC4) and LTD4 concentration-response curves, but no effect on LTE4-induced contractions. Similar results were obtained in preparations from ovalbumin-sensitized animals. 3 Responses produced by 5-HT or U-44069 were similar in the presence and absence of the epithelium in control guinea-pigs. 4 Indomethacin produced contrasting effects on leukotriene-induced contractions in control guinea-pigs: an increase in sensitivity to LTC4 in the presence but not absence of the epithelium, no effect on LTD4-induced contractions and a decrease in sensitivity to LTE4 in both epithelium-containing and epithelium-free preparations. 5 These results indicate that there is selectivity in the effects of epithelium removal on agonist-induced contractions of the guinea-pig trachea. This provides further evidence for the modulatory influence of the epithelium on the reactivity of mammalian airway smooth muscle and supports the postulated existence of an epithelium-derived inhibitory factor. The observation that in intact trachea indomethacin mimics the effects of epithelium removal on LTC4-induced responses, suggests the involvement of a prostanoid(s) in this phenomenon.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adams G. K., 3rd, Lichtenstein L. In vitro studies of antigen-induced bronchospasm: effect of antihistamine and SRS-A antagonist on response of sensitized guinea pig and human airways to antigen. J Immunol. 1979 Feb;122(2):555–562. [PubMed] [Google Scholar]
- 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]
- Cheng J. B., Lang D., Bewtra A., Townley R. G. Tissue distribution and functional correlation of [3H]leukotriene C4 and [3H]leukotriene D4 binding sites in guinea-pig uterus and lung preparations. J Pharmacol Exp Ther. 1985 Jan;232(1):80–87. [PubMed] [Google Scholar]
- Cheng J. B., Townley R. G. Decreased sensitivity and response of isolated tracheal muscle to methacholine and histamine without changing the activity of pulmonary muscarinic receptors in the egg albumin-sensitized guinea pig. Int Arch Allergy Appl Immunol. 1983;72(4):303–309. doi: 10.1159/000234888. [DOI] [PubMed] [Google Scholar]
- Cohen M. L., Schenck K. W., Colbert W., Wittenauer L. Role of 5-HT2 receptors in serotonin-induced contractions of nonvascular smooth muscle. J Pharmacol Exp Ther. 1985 Mar;232(3):770–774. [PubMed] [Google Scholar]
- Creese B. R., Bach M. K., Fitzpatrick F. A., Bothwell W. M. Leukotriene-induced contraction and thromboxane production in guinea-pig lung parenchymal strips. Eur J Pharmacol. 1984 Jul 13;102(2):197–204. doi: 10.1016/0014-2999(84)90251-6. [DOI] [PubMed] [Google Scholar]
- Farmer S. G., Fedan J. S., Hay D. W., Raeburn D. The effects of epithelium removal on the sensitivity of guinea-pig isolated trachealis to bronchodilator drugs. Br J Pharmacol. 1986 Oct;89(2):407–414. doi: 10.1111/j.1476-5381.1986.tb10274.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Fleisch J. H., Rinkema L. E., Marshall W. S. Pharmacologic receptors for the leukotrienes. Biochem Pharmacol. 1984 Dec 15;33(24):3919–3922. doi: 10.1016/0006-2952(84)90001-7. [DOI] [PubMed] [Google Scholar]
- 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]
- Hay D. W., Farmer S. G., Raeburn D., Robinson V. A., Fleming W. W., Fedan J. S. Airway epithelium modulates the reactivity of guinea-pig respiratory smooth muscle. Eur J Pharmacol. 1986 Sep 23;129(1-2):11–18. doi: 10.1016/0014-2999(86)90330-4. [DOI] [PubMed] [Google Scholar]
- Hay D. W., Raeburn D., Farmer S. G., Fleming W. W., Fedan J. S. Epithelium modulates the reactivity of ovalbumin-sensitized guinea-pig airway smooth muscle. Life Sci. 1986 Jun 30;38(26):2461–2468. doi: 10.1016/0024-3205(86)90617-x. [DOI] [PubMed] [Google Scholar]
- Hogaboom G. K., Mong S., Wu H. L., Crooke S. T. Peptidoleukotrienes: distinct receptors for leukotriene C4 and D4 in the guinea-pig lung. Biochem Biophys Res Commun. 1983 Nov 15;116(3):1136–1143. doi: 10.1016/s0006-291x(83)80261-7. [DOI] [PubMed] [Google Scholar]
- Holroyde M. C. The influence of epithelium on the responsiveness of guinea-pig isolated trachea. Br J Pharmacol. 1986 Mar;87(3):501–507. doi: 10.1111/j.1476-5381.1986.tb10192.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Mong S., Hoffman K., Wu H. L., Crooke S. T. Leukotriene-induced hydrolysis of inositol lipids in guinea pig lung: mechanism of signal transduction for leukotriene-D4 receptors. Mol Pharmacol. 1987 Jan;31(1):35–41. [PubMed] [Google Scholar]
- Mong S., Wu H. L., Clark M. A., Gleason J. G., Crooke S. T. Leukotriene D4 receptor-mediated synthesis and release of arachidonic acid metabolites in guinea pig lung: induction of thromboxane and prostacyclin biosynthesis by leukotriene D4. J Pharmacol Exp Ther. 1986 Oct;239(1):63–70. [PubMed] [Google Scholar]
- 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]
- Raeburn D., Hay D. W., Robinson V. A., Farmer S. G., Fleming W. W., Fedan J. S. The effect of verapamil is reduced in isolated airway smooth muscle preparations lacking the epithelium. Life Sci. 1986 Mar 3;38(9):809–816. doi: 10.1016/0024-3205(86)90597-7. [DOI] [PubMed] [Google Scholar]
- Snyder D. W., Aharony D., Dobson P., Tsai B. S., Krell R. D. Pharmacological and biochemical evidence for metabolism of peptide leukotrienes by guinea-pig airway smooth muscle in vitro. J Pharmacol Exp Ther. 1984 Nov;231(2):224–229. [PubMed] [Google Scholar]