Abstract
1. The effect of removing the epithelium on the responses of the guinea-pig isolated trachea (GPT) to bradykinin (BK) and prostaglandin E2 (PGE2) was investigated. 2. BK (3 pmol-10 nmol) induced dose-related relaxations of the intact (with epithelium), and contracted the rubbed (without epithelium) preparation of GPT. Similar responses were also obtained with PGE2 (0.3-3.0 nmol). 3. Indomethacin (1.4 microM) modified the BK-induced response of intact GPT, from a relaxation to a contraction, but inhibited the BK-induced contraction of the rubbed GPT. 4. There was a significant increase in PGE2 release from the intact GPT following stimulation with BK. 5. Removal of the epithelium from the GPT significantly reduced both basal and BK-induced generation of PGE2. 6. The induction of tone in the rubbed GPT by addition of acetylcholine (ACh) caused BK and PGE2 (0.3 nmol-3 nmol) to produce relaxations of the tissue. 7. Salbutamol (10(-8) M-10(-6) M) reduced the relaxations induced by BK on intact GPT, in a concentration-dependent manner. 8. These results suggest that both tone and an epithelial-dependent cyclo-oxygenase mechanism are important in modulating BK-induced responses of GPT.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bramley A. M., Samhoun M. N., Piper P. J. Effect of a bradykinin B2 antagonist on responses of intact and rubbed guinea-pig trachea in vitro. Br J Pharmacol. 1989 Dec;98 (Suppl):786P–786P. [PubMed] [Google Scholar]
- Braunstein G., Labat C., Brunelleschi S., Benveniste J., Marsac J., Brink C. Evidence that the histamine sensitivity and responsiveness of guinea-pig isolated trachea are modulated by epithelial prostaglandin E2 production. Br J Pharmacol. 1988 Sep;95(1):300–308. doi: 10.1111/j.1476-5381.1988.tb16577.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cantwell M. E., Foreman J. C. The actions of inhibitors of diacylglycerol kinase and diacylglycerol lipase on histamine release from rat peritoneal mast cells. Br J Pharmacol. 1987 Nov;92(3):597–601. doi: 10.1111/j.1476-5381.1987.tb11361.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Emmerson J., Mackay D. The zig-zag tracheal strip. J Pharm Pharmacol. 1979 Nov;31(11):798–798. doi: 10.1111/j.2042-7158.1979.tb13666.x. [DOI] [PubMed] [Google Scholar]
- Farmer S. G., Hay D. W., Raeburn D., Fedan J. S. Relaxation of guinea-pig tracheal smooth muscle to arachidonate is converted to contraction following epithelium removal. Br J Pharmacol. 1987 Sep;92(1):231–236. doi: 10.1111/j.1476-5381.1987.tb11316.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]
- Folkers K., Håkanson R., Hörig J., Xu J. C., Leander S. Biological evaluation of substance P antagonists. Br J Pharmacol. 1984 Oct;83(2):449–456. doi: 10.1111/j.1476-5381.1984.tb16506.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Folkerts G., Engels F., Nijkamp F. P. Endotoxin-induced hyperreactivity of the guinea-pig isolated trachea coincides with decreased prostaglandin E2 production by the epithelial layer. Br J Pharmacol. 1989 Feb;96(2):388–394. doi: 10.1111/j.1476-5381.1989.tb11829.x. [DOI] [PMC free article] [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., 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]
- Hay D. W., Muccitelli R. M., Horstemeyer D. L., Raeburn D. Is the epithelium-derived inhibitory factor in guinea-pig trachea a prostanoid? Prostaglandins. 1988 Apr;35(4):625–637. doi: 10.1016/0090-6980(88)90036-6. [DOI] [PubMed] [Google Scholar]
- Hay D. W., Muccitelli R. M., Horstemeyer D. L., Wilson K. A., Raeburn D. Demonstration of the release of an epithelium-derived inhibitory factor from a novel preparation of guinea-pig trachea. Eur J Pharmacol. 1987 Apr 14;136(2):247–250. doi: 10.1016/0014-2999(87)90719-9. [DOI] [PubMed] [Google Scholar]
- Hay D. W., Muccitelli R. M., Tucker S. S., Vickery-Clark L. M., Wilson K. A., Gleason J. G., Hall R. F., Wasserman M. A., Torphy T. J. Pharmacologic profile of SK&F 104353: a novel, potent and selective peptidoleukotriene receptor antagonist in guinea pig and human airways. J Pharmacol Exp Ther. 1987 Nov;243(2):474–481. [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]
- Jose P., Niederhauser U., Piper P. J., Robinson C., Smith A. P. Degradation of porstaglandin F2alpha in the human pulmonary circulation. Thorax. 1976 Dec;31(6):713–719. doi: 10.1136/thx.31.6.713. [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]
- Lumley P., White B. P., Humphrey P. P. GR32191, a highly potent and specific thromboxane A2 receptor blocking drug on platelets and vascular and airways smooth muscle in vitro. Br J Pharmacol. 1989 Jul;97(3):783–794. doi: 10.1111/j.1476-5381.1989.tb12017.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mizrahi J., D'Orléans-Juste P., Caranikas S., Regoli D. Effects of peptides and amines on isolated guinea pig tracheae as influenced by inhibitors of the metabolism of arachidonic acid. Pharmacology. 1982;25(6):320–326. doi: 10.1159/000137758. [DOI] [PubMed] [Google Scholar]
- Nijkamp F. P., Folkerts G. Reversal of arachidonic acid-induced guinea-pig tracheal relaxation into contraction after epithelium removal. Eur J Pharmacol. 1986 Nov 19;131(2-3):315–316. doi: 10.1016/0014-2999(86)90591-1. [DOI] [PubMed] [Google Scholar]
- Piper P. J., Vane J. R. Release of additional factors in anaphylaxis and its antagonism by anti-inflammatory drugs. Nature. 1969 Jul 5;223(5201):29–35. doi: 10.1038/223029a0. [DOI] [PubMed] [Google Scholar]
- Raeburn D., Hay D. W., Muccitelli R. M., Dey R. D., Fedan J. S. The development of tone in the smooth muscle of guinea-pig isolated tracheal preparations may be influenced by prostanoids released from the adjacent airway cartilage. Prostaglandins. 1987 May;33(5):651–661. doi: 10.1016/0090-6980(87)90032-3. [DOI] [PubMed] [Google Scholar]
- 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]
