Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1983 Jan;78(1):67–74. doi: 10.1111/j.1476-5381.1983.tb09363.x

An in vivo model for measuring antigen-induced SRS-A-mediated bronchoconstriction and plasma SRS-A levels in the guinea-pig.

W H Anderson, M O'Donnell, B A Simko, A F Welton
PMCID: PMC2044773  PMID: 6824817

Abstract

1 Pharmacological modulation of antigen-induced anaphylaxis in actively sensitized guinea-pigs with intravenously administered indomethacin (10 mg/kg), pyrilamine (2.0 mg/kg) and propranolol (0.1 mg/kg) resulted in a delayed onset, slowly developing bronchoconstriction indicative of a slow-reacting substance of anaphylaxis (SRS-A) response. 2 Measurements of pulmonary mechanics on the drug-pretreated animals challenged with ovalbumin demonstrated a more prominent effect on dynamic compliance than resistance. This is consistent with the more potent effects of SRS-A on peripheral rather than central airways. 3 The slowly developing bronchoconstriction obtained after treatment with indomethacin, pyrilamine and propranolol was inhibited by the standard SRS-A antagonist, FPL 55712 and the SRS-A synthesis inhibitors, phenidone, BW 755C and nordihydroguaiaretic acid. 4 Plasma SRS-A levels were determined in guinea-pigs following antigen challenge. The appearance of SRS-A in the plasma preceded the onset of bronchoconstriction and SRS-A levels remained elevated throughout its development. Coincident with the inhibition of bronchoconstriction by the SRS-A synthesis inhibitor, phenidone, was a dose-dependent reduction in plasma SRS-A. The intravenous ED50 in each case was 4 mg/kg. 5 This model of antigen-induced SRS-A-mediated bronchoconstriction should prove useful for the in vivo evaluation and development of therapeutics which regulate the synthesis of SRS-A.

Full text

PDF

Selected References

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

  1. AMDUR M. O., MEAD J. Mechanics of respiration in unanesthetized guinea pigs. Am J Physiol. 1958 Feb;192(2):364–368. doi: 10.1152/ajplegacy.1958.192.2.364. [DOI] [PubMed] [Google Scholar]
  2. Armour C. L., Hughes J. M., Seale J. P., Temple D. M. Effect of lipoxygenase inhibitors on release of slow-reacting substances from human lung. Eur J Pharmacol. 1981 Jun 10;72(1):93–96. doi: 10.1016/0014-2999(81)90302-2. [DOI] [PubMed] [Google Scholar]
  3. Augstein J., Farmer J. B., Lee T. B., Sheard P., Tattersall M. L. Selective inhibitor of slow reacting substance of anaphylaxis. Nat New Biol. 1973 Oct 17;245(146):215–217. doi: 10.1038/newbio245215a0. [DOI] [PubMed] [Google Scholar]
  4. Austen K. F. Homeostasis of effector systems which can also be recruited for immunologic reactions. J Immunol. 1978 Sep;121(3):793–805. [PubMed] [Google Scholar]
  5. Austen K. F., Orange R. P. Bronchial asthma: the possible role of the chemical mediators of immediate hypersensitivity in the pathogenesis of subacute chronic disease. Am Rev Respir Dis. 1975 Sep;112(3):423–436. doi: 10.1164/arrd.1975.112.3.423. [DOI] [PubMed] [Google Scholar]
  6. Bach M. K., Brashler J. R., Brooks C. D., Neerken A. J. Slow reacting substances: comparison of some properties of human lung SRS-A and two distinct fractions from ionophore-induced rat mononuclear cell SRS. J Immunol. 1979 Jan;122(1):160–165. [PubMed] [Google Scholar]
  7. Blackwell G. J., Flower R. J. 1-phenyl-3-pyrazolidone: an inhibitor of cyclo-oxygenase and lipoxygenase pathways in lung and platelets. Prostaglandins. 1978 Sep;16(3):417–425. doi: 10.1016/0090-6980(78)90220-4. [DOI] [PubMed] [Google Scholar]
  8. Burka J. F., Flower R. J. Effects of modulators of arachidonic acid metabolism on the synthesis and release of slow-reacting substance of anaphylaxis. Br J Pharmacol. 1979 Jan;65(1):35–41. doi: 10.1111/j.1476-5381.1979.tb17331.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chand N. FPL 55712 -- an antagonist of slow reacting substance of anaphylaxis (SRS-A): a review. Agents Actions. 1979 Jun;9(2):133–140. doi: 10.1007/BF02024724. [DOI] [PubMed] [Google Scholar]
  10. Colebatch H. J., Olsen C. R., Nadel J. A. Effect of histamine, serotonin, and acetylcholine on the peripheral airways. J Appl Physiol. 1966 Jan;21(1):217–226. doi: 10.1152/jappl.1966.21.1.217. [DOI] [PubMed] [Google Scholar]
  11. Collier H. O., James G. W. Humoral factors affecting pulmonary inflation during acute anaphylaxis in the guinea-pig in vivo. Br J Pharmacol Chemother. 1967 Jun;30(2):283–301. doi: 10.1111/j.1476-5381.1967.tb02135.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dahlén S. E., Hedqvist P., Hammarström S., Samuelsson B. Leukotrienes are potent constrictors of human bronchi. Nature. 1980 Dec 4;288(5790):484–486. doi: 10.1038/288484a0. [DOI] [PubMed] [Google Scholar]
  13. Drazen J. M., Austen K. F. Effects of intravenous administration of slow-reacting substance of anaphylaxis, histamine, bradykinin, and prostaglandin F2alpha on pulmonary mechanics in the guinea pig. J Clin Invest. 1974 Jun;53(6):1679–1685. doi: 10.1172/JCI107719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Drazen J. M., Austen K. F., Lewis R. A., Clark D. A., Goto G., Marfat A., Corey E. J. Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4354–4358. doi: 10.1073/pnas.77.7.4354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Engineer D. M., Niederhauser U., Piper P. J., Sirois P. Release of mediators of anaphylaxis: inhibition of prostaglandin synthesis and the modification of release of slow reacting substance of anaphylaxis and histamine. Br J Pharmacol. 1978 Jan;62(1):61–66. doi: 10.1111/j.1476-5381.1978.tb07006.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Goetzl E. J. Mediators of immediate hypersensitivity derived from arachidonic acid. N Engl J Med. 1980 Oct 2;303(14):822–825. doi: 10.1056/NEJM198010023031421. [DOI] [PubMed] [Google Scholar]
  17. Hanna C. J., Bach M. K., Pare P. D., Schellenberg R. R. Slow-reacting substances (leukotrienes) contract human airway and pulmonary vascular smooth muscle in vitro. Nature. 1981 Mar 26;290(5804):343–344. doi: 10.1038/290343a0. [DOI] [PubMed] [Google Scholar]
  18. Hitchcock M. Effect of inhibitors of prostaglandin synthesis and prostaglandins E2 and F2alpha on the immunologic release of mediators of inflammation from actively sensitized guinea-pig lung. J Pharmacol Exp Ther. 1978 Nov;207(2):630–640. [PubMed] [Google Scholar]
  19. Hutchcroft B. J., Orange R. P. The role of calcium in the generation of intracellular SRS-A in passively sensitized human lung challenged with antigen. Clin Allergy. 1980 Sep;10(5):565–573. doi: 10.1111/j.1365-2222.1980.tb02138.x. [DOI] [PubMed] [Google Scholar]
  20. Macklem P. T., Mead J. Resistance of central and peripheral airways measured by a retrograde catheter. J Appl Physiol. 1967 Mar;22(3):395–401. doi: 10.1152/jappl.1967.22.3.395. [DOI] [PubMed] [Google Scholar]
  21. Morris H. R., Taylor G. W., Piper P. J., Samhoun M. N., Tippins J. R. Slow reacting substances (SRSs): the structure identification of SRSs from rat basophil leukaemia (RBL-1) cells. Prostaglandins. 1980 Feb;19(2):185–201. doi: 10.1016/0090-6980(80)90019-2. [DOI] [PubMed] [Google Scholar]
  22. Orning L., Hammarström S. Inhibition of leukotriene C and leukotriene D biosynthesis. J Biol Chem. 1980 Sep 10;255(17):8023–8026. [PubMed] [Google Scholar]
  23. Parker C. W., Falkenhein S. F., Huber M. M. Sequential conversion of the glutathionyl side chain of slow reacting substance (SRS) to cysteinyl-glycine and cysteine in rat basophilic leukemia cells stimulated with A-23187. Prostaglandins. 1980 Nov;20(5):863–886. doi: 10.1016/0090-6980(80)90139-2. [DOI] [PubMed] [Google Scholar]
  24. Parker C. W., Koch D., Huber M. M., Falkenhein S. F. Formation of the cysteinyl form of slow reacting substance (leukotriene E4) in human plasma. Biochem Biophys Res Commun. 1980 Dec 16;97(3):1038–1046. doi: 10.1016/0006-291x(80)91480-1. [DOI] [PubMed] [Google Scholar]
  25. Paterson N. A., Burka J. F., Craig I. D. Release of slow-reacting substance of anaphylaxis from dispersed pig lung cells: effect of cyclo-oxygenase and lipoxygenase inhibitors. J Allergy Clin Immunol. 1981 Jun;67(6):426–434. doi: 10.1016/0091-6749(81)90095-6. [DOI] [PubMed] [Google Scholar]
  26. Piper P. J., Temple D. M. The effect of lipoxygenase inhibitors and diethylcarbamazine on the immunological release of slow reacting substance of anaphylaxis (SRS-A) from guinea-pig chopped lung. J Pharm Pharmacol. 1981 Jun;33(6):384–386. doi: 10.1111/j.2042-7158.1981.tb13810.x. [DOI] [PubMed] [Google Scholar]
  27. Richardson J. B., Hogg J. C., Bouchard T., Hall D. L. Localization of antigen in experimental bronchoconstriction in guinea pigs. J Allergy Clin Immunol. 1973 Sep;52(3):172–181. doi: 10.1016/0091-6749(73)90034-1. [DOI] [PubMed] [Google Scholar]
  28. Ritchie D. M., Sierchio J. N., Capetola R. J., Rosenthale M. E. SRS-A mediated bronchospasm by pharmacologic modification of lung anaphylaxis in vivo. Agents Actions. 1981 Jul;11(4):396–401. doi: 10.1007/BF01982477. [DOI] [PubMed] [Google Scholar]
  29. Samuelsson B., Hammarström S., Murphy R. C., Borgeat P. Leukotrienes and slow reacting substance of anaphylaxis (SRS-A). Allergy. 1980 Jul;35(5):375–381. doi: 10.1111/j.1398-9995.1980.tb01782.x. [DOI] [PubMed] [Google Scholar]
  30. Sirois P., Borgeat P. From slow reacting substance of anaphylaxis (SRS-A) to leukotriene D4 (LTD4). Int J Immunopharmacol. 1980;2(4):281–293. doi: 10.1016/0192-0561(80)90028-4. [DOI] [PubMed] [Google Scholar]
  31. Walker J. R., Boot J. R., Cox B., Dawson W. Inhibition of the release of slow-reacting substance of anaphylaxis by inhibitors of lipoxygenase activity. J Pharm Pharmacol. 1980 Dec;32(12):866–867. doi: 10.1111/j.2042-7158.1980.tb13096.x. [DOI] [PubMed] [Google Scholar]
  32. Welton A. F., Crowley H. J., Miller D. A., Yaremko B. Biological activities of a chemically synthesized form of leukotriene E4. Prostaglandins. 1981 Feb;21(2):287–296. doi: 10.1016/0090-6980(81)90146-5. [DOI] [PubMed] [Google Scholar]
  33. Welton A. F., Hope W. C., Tobias L. D., Hamilton J. G. Inhibition of antigen-induced histamine release and thromboxane synthase by FPL 55712, a specific SRA-A antagonist? Biochem Pharmacol. 1981 Jun 1;30(11):1378–1382. doi: 10.1016/0006-2952(81)90328-2. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES