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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1988 Apr;93(4):751–758. doi: 10.1111/j.1476-5381.1988.tb11459.x

Release of arachidonic acid metabolites and histamine from sensitized guinea-pig lung following antigen challenge.

N C Turner 1, C T Dollery 1
PMCID: PMC1853874  PMID: 2455578

Abstract

1. The time course of mediator release and the hypothesis that the ratio of eicosanoids to histamine might alter with the intensity of stimulus or its route of administration has been explored in isolated perfused lung from sensitized guinea-pigs challenged with ovalbumin. 2. Histamine and prostaglandin release was rapid in onset and virtually complete within 10 min. Thromboxane B2 (TXB2) and leukotriene D4 (LTD4) release, however, was more sustained. Release of the major prostanoid metabolites was relatively delayed compared to that of the parent compounds and was more sustained. 3. Mediator release was antigen-dose dependent and TXB2, prostaglandin D2 (PGD2) and LTD4 release linearly related to histamine concentrations (P less than 0.05). However, the ratio of the percentage maximum release of eicosanoids relative to histamine was greatest with low doses of ovalbumin. 4. At a low antigen dose (10 micrograms ovalbumin), histamine and prostanoid release was greatest when the challenge was via the airway rather than into the pulmonary artery and the greatest differences were in PGF2 alpha levels. At near maximal challenge (1 mg ovalbumin) there was little difference in concentrations of PGD2, TXB2, 6-oxo-PGF1 alpha and LTD4 by either route, but PGF2 alpha levels remained greater. 5. The results indicate that biologically active amounts of prostanoids may be released from sensitized lung at low degrees of mast cell activation and that differences in mediator release following antigen administration to the airway or into the pulmonary vasculature simply reflects its accessibility to sensitized cells.

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Selected References

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

  1. Adams G. K., 3rd, Lichtenstein L. M. Indomethacin enhances response of human bronchus to antigen. Am Rev Respir Dis. 1985 Jan;131(1):8–10. doi: 10.1164/arrd.1985.131.1.8. [DOI] [PubMed] [Google Scholar]
  2. Andersson P. Effects of inhibitors of anaphylactic mediators in two models of bronchial anaphylaxis in anaesthetized guinea-pigs. Br J Pharmacol. 1982 Oct;77(2):301–307. doi: 10.1111/j.1476-5381.1982.tb09299.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bakhle Y. S., Moncada S., de Nucci G., Salmon J. A. Differential release of eicosanoids by bradykinin, arachidonic acid and calcium ionophore A23187 in guinea-pig isolated perfused lung. Br J Pharmacol. 1985 Sep;86(1):55–62. doi: 10.1111/j.1476-5381.1985.tb09434.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berti F., Folco G. C., Nicosia S., Omini C., Pasargiklian R. The role of histamine H1- and H2-receptors in the generation of thromboxane A2 in perfused guinea-pig lungs. Br J Pharmacol. 1979 Apr;65(4):629–633. doi: 10.1111/j.1476-5381.1979.tb07874.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burka J. F. Effect of indomethacin on airway contraction and the release of LTC4-like material. Prostaglandins. 1985 Apr;29(4):529–535. doi: 10.1016/0090-6980(85)90077-2. [DOI] [PubMed] [Google Scholar]
  6. Burka J. F. Pharmacological modulation of responses of guinea-pig airways contracted with antigen and calcium ionophore A23187. Br J Pharmacol. 1985 Jun;85(2):411–420. doi: 10.1111/j.1476-5381.1985.tb08876.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Engineer D. M., Morris H. R., Piper P. J., Sirois P. The release of prostaglandins and thromboxanes from guinea-pig lung by slow reacting substance of anaphylaxis, and its inhibition. Br J Pharmacol. 1978 Oct;64(2):211–218. doi: 10.1111/j.1476-5381.1978.tb17291.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Håkanson R., Rönnberg A. L., Sjölund K. Fluorometric determination of histamine with OPT: optimum reaction conditions and tests of identity. Anal Biochem. 1972 Jun;47(2):356–370. doi: 10.1016/0003-2697(72)90129-7. [DOI] [PubMed] [Google Scholar]
  9. Kagey-Sobotka A., MacGlashan D. W., Lichtenstein L. M. Role of receptor aggregation in triggering IgE-mediated reactions. Fed Proc. 1982 Jan;41(1):12–16. [PubMed] [Google Scholar]
  10. Lewis R. A., Soter N. A., Diamond P. T., Austen K. F., Oates J. A., Roberts L. J., 2nd Prostaglandin D2 generation after activation of rat and human mast cells with anti-IgE. J Immunol. 1982 Oct;129(4):1627–1631. [PubMed] [Google Scholar]
  11. Mathé A. A., Hedqvist P., Strandberg K., Leslie C. A. Aspects of prostaglandin function in the lung (first of two parts). N Engl J Med. 1977 Apr 14;296(15):850–855. doi: 10.1056/NEJM197704142961505. [DOI] [PubMed] [Google Scholar]
  12. Ogunbiyi P. O., Eyre P. Pharmacological studies of pulmonary anaphylaxis in vitro: a review. Agents Actions. 1985 Dec;17(2):158–174. doi: 10.1007/BF01966586. [DOI] [PubMed] [Google Scholar]
  13. Peters S. P., MacGlashan D. W., Jr, Schleimer R. P., Hayes E. C., Adkinson N. F., Jr, Lichtenstein L. M. The pharmacologic modulation of the release of arachidonic acid metabolites from purified human lung mast cells. Am Rev Respir Dis. 1985 Aug;132(2):367–373. doi: 10.1164/arrd.1985.132.2.367. [DOI] [PubMed] [Google Scholar]
  14. Piper P. J., Samhoun M. N. Stimulation of arachidonic acid metabolism and generation of thromboxane A2 by leukotrienes B4, C4 and D4 in guinea-pig lung in vitro. Br J Pharmacol. 1982 Oct;77(2):267–275. doi: 10.1111/j.1476-5381.1982.tb09295.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Richmond R., Turner N. C., Maltby N., Heavey D., Vial J., Dollery C. T., Taylor G. W. Single-step procedure for the extraction and purification of leukotrienes B4, C4 and D4. J Chromatogr. 1987 Jul 3;417(2):241–251. doi: 10.1016/0378-4347(87)80117-2. [DOI] [PubMed] [Google Scholar]
  17. Robinson C., Hoult J. R. Inactivation of prostaglandins in the perfused rat lung. Biochem Pharmacol. 1982 Mar 1;31(5):633–638. doi: 10.1016/0006-2952(82)90442-7. [DOI] [PubMed] [Google Scholar]
  18. Schulman E. S., Newball H. H., Demers L. M., Fitzpatrick F. A., Adkinson N. F., Jr Anaphylactic release of thromboxane A2, prostaglandin D2, and prostacyclin from human lung parenchyma. Am Rev Respir Dis. 1981 Oct;124(4):402–406. doi: 10.1164/arrd.1981.124.4.402. [DOI] [PubMed] [Google Scholar]
  19. Waddell K. A., Barrow S. E., Robinson C., Orchard M. A., Dollery C. T., Blair I. A. Quantitative analysis of prostanoids in biological fluids by combined capillary column gas chromatography negative ion chemical ionization mass spectrometry. Biomed Mass Spectrom. 1984 Feb;11(2):68–74. doi: 10.1002/bms.1200110205. [DOI] [PubMed] [Google Scholar]

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