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. 1985 Sep;86(1):55–62. doi: 10.1111/j.1476-5381.1985.tb09434.x

Differential release of eicosanoids by bradykinin, arachidonic acid and calcium ionophore A23187 in guinea-pig isolated perfused lung.

Y S Bakhle, S Moncada, G de Nucci, J A Salmon
PMCID: PMC1916852  PMID: 2996675

Abstract

The effects of infusions of bradykinin (0.2 microM), calcium ionophore A23187 (0.5 microM) and arachidonic acid (13 microM) on the release of eicosanoids from the guinea-pig isolated perfused lung were investigated using radioimmunoassay for thromboxane B2 (TXB2), 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha), PGE2, leukotriene B4 (LTB4) and LTC4 and bioassay using the superfusion cascade. Bradykinin released more 6-oxo-PGF1 alpha than TXB2, whereas arachidonic acid and ionophore released more TXB2 than 6-oxo-PGF1 alpha. The time course of eicosanoid release varied with the stimulus: bradykinin and arachidonic acid produced an immediate release, whereas the ionophore showed a slower onset of release. Although the amounts of LTB4 and LTC4 released by the ionophore were very low according to radioimmunoassays, there was evidence from the bioassay of release of a leukotriene-like substance, thought to be LTD4. The leukotriene antagonist FPL 55712 lacks specificity in the guinea-pig trachea; at the concentration used (2 microM) it antagonized contractions of the tracheal strip to PGE2 as well as to LTC4. Our results show that in the guinea-pig perfused lung the metabolism of exogenous arachidonic acid is both qualitatively and quantitatively different from the metabolism of endogenous arachidonic acid; furthermore, the profile of eicosanoid production is stimulus-dependent.

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Selected References

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  1. Aehringhaus U., Wölbling R. H., König W., Patrono C., Peskar B. M., Peskar B. A. Release of leukotriene C4 from human polymorphonuclear leucocytes as determined by radioimmunoassay. FEBS Lett. 1982 Sep 6;146(1):111–114. doi: 10.1016/0014-5793(82)80715-1. [DOI] [PubMed] [Google Scholar]
  2. Al-Ubaidi F., Bakhle Y. S. Differences in biological activation of arachidonic acid in perfused lungs from guinea pig, rat and man. Eur J Pharmacol. 1980 Mar 7;62(1):89–96. doi: 10.1016/0014-2999(80)90484-7. [DOI] [PubMed] [Google Scholar]
  3. Ally A. I., Boucher R., Knowles M. R., Eling T. E. Metabolism of prostaglandin endoperoxide by microsomes from human lung parenchyma and comparison with metabolites produced by pig, bovine, rat, mouse and guinea-pig. Prostaglandins. 1982 Oct;24(4):575–584. doi: 10.1016/0090-6980(82)90015-6. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Bakhle Y. S., Reynard A. M., Vane J. R. Metabolism of the angiotensins in isolated perfused tissues. Nature. 1969 Jun 7;222(5197):956–959. doi: 10.1038/222956a0. [DOI] [PubMed] [Google Scholar]
  6. Boot J. R., Cockerill A. F., Dawson W., Mallen D. N., Osborne D. J. Modification of prostaglandin and thromboxane release by immunological sensitisation and successive immunological challenges from guinea-pig lumg. Int Arch Allergy Appl Immunol. 1978;57(2):159–164. doi: 10.1159/000232097. [DOI] [PubMed] [Google Scholar]
  7. Burka J. F., Saad M. H. Mediators of arachidonic acid-induced contractions of indomethacin-treated guinea-pig airways: leukotrienes C4 and D4. Br J Pharmacol. 1984 Mar;81(3):465–473. doi: 10.1111/j.1476-5381.1984.tb10099.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Crutchley D. J., Ryan J. W., Ryan U. S., Fisher G. H. Bradykinin-induced release of prostacyclin and thromboxanes from bovine pulmonary artery endothelial cells. Studies with lower homologs and calcium antagonists. Biochim Biophys Acta. 1983 Mar 22;751(1):99–107. doi: 10.1016/0005-2760(83)90261-8. [DOI] [PubMed] [Google Scholar]
  9. Dawson W., Boot J. R., Cockerill A. F., Mallen D. N., Osborne D. J. Release of novel prostaglandins and thromboxanes after immunological challenge of guinea pig lung. Nature. 1976 Aug 19;262(5570):699–702. doi: 10.1038/262699a0. [DOI] [PubMed] [Google Scholar]
  10. Eckenfels A., Vane J. R. Prostaglandins, oxygen tension and smooth muscle tone. Br J Pharmacol. 1972 Jul;45(3):451–462. doi: 10.1111/j.1476-5381.1972.tb08101.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gilmore N., Vane J. R., Wyllie J. H. Prostaglandins released by the spleen. Nature. 1968 Jun 22;218(5147):1135–1140. doi: 10.1038/2181135a0. [DOI] [PubMed] [Google Scholar]
  12. Gryglewski R. J., Korbut R., Ocetkiewicz A., Spławiński J., Wojtaszek B., Swies J. Lungs as a generator of prostacyclin--hypothesis on physiological significance. Naunyn Schmiedebergs Arch Pharmacol. 1978 Aug;304(1):45–50. doi: 10.1007/BF00501376. [DOI] [PubMed] [Google Scholar]
  13. Hamberg M., Svensson J., Hedqvist P., Strandberg K., Samuelsson B. Involvement of endoperoxides and thromboxanes in anaphylactic reactions. Adv Prostaglandin Thromboxane Res. 1976;1:495–501. [PubMed] [Google Scholar]
  14. Ingerman-Wojenski C., Silver M. J., Smith J. B., Macarak E. Bovine endothelial cells in culture produce thromboxane as well as prostacyclin. J Clin Invest. 1981 May;67(5):1292–1296. doi: 10.1172/JCI110157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Isakson P. C., Raz A., Needleman P. Selective incorporation of 14C-arachidonic acid into the phospholipids of intact tissues and subsequent metabolism to 14C-prostaglandins. Prostaglandins. 1976 Nov;12(5):739–748. doi: 10.1016/0090-6980(76)90049-6. [DOI] [PubMed] [Google Scholar]
  16. Morris H. R., Taylor G. W., Jones C. M., Piper P. J., Samhoun M. N., Tippins J. R. Slow reacting substances (leukotrienes): enzymes involved in their biosynthesis. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4838–4842. doi: 10.1073/pnas.79.16.4838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Needleman P., Wyche A., Bronson S. D., Holmberg S., Morrison A. R. Specific regulation of peptide-induced renal prostaglandin synthesis. J Biol Chem. 1979 Oct 10;254(19):9772–9779. [PubMed] [Google Scholar]
  18. PATON W. D. A pendulum auxotonic lever. J Physiol. 1957 Jul 11;137(2):35P–356. [PubMed] [Google Scholar]
  19. Palmer M. A., Piper P. J., Vane J. R. Release of rabbit aorta contracting substance (RCS) and prostaglandins induced by chemical or mechanical stimulation of guinea-pig lungs. Br J Pharmacol. 1973 Oct;49(2):226–242. doi: 10.1111/j.1476-5381.1973.tb08368.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Piper P. J., Seale J. P. Non-immunological release of slow-reacting substance from guinea-pig lungs. Br J Pharmacol. 1979 Sep;67(1):67–72. [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Robinson C., Hoult J. R., Waddell K. A., Blair I. A., Dollery C. T. Total profiling by GC/NICIMS of the major cyclo-oxygenase products from antigen and leukotriene-challenged guinea-pig lung. Biochem Pharmacol. 1984 Feb 1;33(3):395–400. doi: 10.1016/0006-2952(84)90231-4. [DOI] [PubMed] [Google Scholar]
  23. Saldeen P., Saldeen T. 6-keto-prostaglandin F1 alpha/thromboxane B2 ratio in vascular and lung tissue. Thromb Res. 1983 Jun 15;30(6):643–650. doi: 10.1016/0049-3848(83)90273-6. [DOI] [PubMed] [Google Scholar]
  24. Salmon J. A. A radioimmunoassay for 6-keto-prostaglandin F1alpha. Prostaglandins. 1978 Mar;15(3):383–397. doi: 10.1016/0090-6980(78)90122-3. [DOI] [PubMed] [Google Scholar]
  25. Salmon J. A., Simmons P. M., Palmer R. M. A radioimmunoassay for leukotriene B4. Prostaglandins. 1982 Aug;24(2):225–235. doi: 10.1016/0090-6980(82)90148-4. [DOI] [PubMed] [Google Scholar]
  26. Salzman P. M., Salmon J. A., Moncada S. Prostacyclin and thromboxane A2 synthesis by rabbit pulmonary artery. J Pharmacol Exp Ther. 1980 Oct;215(1):240–247. [PubMed] [Google Scholar]
  27. Sirois P., Brousseau Y. Leukotriene transformation by guinea-pig lungs. Prostaglandins Leukot Med. 1983 Feb;10(2):133–143. doi: 10.1016/s0262-1746(83)80004-3. [DOI] [PubMed] [Google Scholar]
  28. VANE J. R. THE USE OF ISOLATED ORGANS FOR DETECTING ACTIVE SUBSTANCES IN THE CIRCULATING BLOOD. Br J Pharmacol Chemother. 1964 Oct;23:360–373. doi: 10.1111/j.1476-5381.1964.tb01592.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]

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