Skip to main content
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1992;1(4):255–261. doi: 10.1155/S0962935192000395

Cyclic-AMP mediated drugs: differential or global reduction of eicosanoid synthesis in the isolated rat lung?

Mark J Post 3,, Jan Dirk te Biesebeek 2, Johan Wemer 3, Hans H van Rooij 2, Freek J Zijlstra 1, Arijan J Porsius 2
PMCID: PMC2365352  PMID: 18475470

Abstract

In this study the question was addressed whether cAMP mediated drugs induce a differential reduction of branches of the arachidonic acid metabolism rather than a global reduction of eicosanoid synthesis. The isolated lungs of actively sensitized rats were employed to study prostaglandin and leukotriene release in the presence and absence of the cAMP mediated drugs theophylline, milrinone, sulmazole, isobutyl-methylxanthine and salbutamol. The release of eicosanoids as measured by RIA was predominantly basal and continuous, with a mild antigen induced stimulation only for TXB2 and the leukotrienes. All drugs reduced eicosanoid release globally. It is concluded that cAMP mediated drugs interfere with arachidonic acid metabolism at a site proximal to the branching into lipoxygenase and cyclo-oxygenase pathways.

Full Text

The Full Text of this article is available as a PDF (629.2 KB).

Selected References

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

  1. Beavo J. A., Reifsnyder D. H. Primary sequence of cyclic nucleotide phosphodiesterase isozymes and the design of selective inhibitors. Trends Pharmacol Sci. 1990 Apr;11(4):150–155. doi: 10.1016/0165-6147(90)90066-H. [DOI] [PubMed] [Google Scholar]
  2. Brunet G., Piechuta H., Hamel R., Holme G., Ford-Hutchinson A. W. Respiratory responses to leukotrienes and biogenic amines in normal and hyperreactive rats. J Immunol. 1983 Jul;131(1):434–438. [PubMed] [Google Scholar]
  3. Cohan V., McKenzie-White J., Triggiani M., Massey W., Kagey-Sobotka A., Lichtenstein L. M. Heterogeneity of human mast cells and basophils. Effects of a putative 5-lipoxygenase inhibitor. Biochem Pharmacol. 1989 Dec 15;38(24):4455–4459. doi: 10.1016/0006-2952(89)90656-4. [DOI] [PubMed] [Google Scholar]
  4. Grupe R. Lipoxygenasekatalysierter Arachidonsäuremetabolismus und Auswirkungen seiner Inhibition auf anaphylaktische Reaktionen. Pharmazie. 1986 Jan;41(1):7–22. [PubMed] [Google Scholar]
  5. Hanley S. P. Prostaglandins and the lung. Lung. 1986;164(2):65–77. doi: 10.1007/BF02713630. [DOI] [PubMed] [Google Scholar]
  6. Ikeda U., Toyo-oka T., Arisaka H., Hosoda S. Stimulated synthesis of prostaglandin E2 or leukotrien C4 from myocardial cells is not a cause but a result of their injury under hypoxia. J Mol Cell Cardiol. 1987 Jun;19(6):523–526. doi: 10.1016/s0022-2828(87)80359-0. [DOI] [PubMed] [Google Scholar]
  7. Mita H., Yui Y., Shida T. Effect of AA-861, a 5-lipoxygenase inhibitor, on leukotriene synthesis in human polymorphonuclear leukocytes and on cyclooxygenase and 12-lipoxygenase activities in human platelets. Allergy. 1986 Sep;41(7):493–498. doi: 10.1111/j.1398-9995.1986.tb00334.x. [DOI] [PubMed] [Google Scholar]
  8. Orange R. P., Kaliner M. A., Laraia P. J., Austen K. F. Immunological release of histamine and slow reacting substance of anaphylaxis from human lung. II. Influence of cellular levels of cyclic AMP. Fed Proc. 1971 Nov-Dec;30(6):1725–1729. [PubMed] [Google Scholar]
  9. Peachell P. T., MacGlashan D. W., Jr, Lichtenstein L. M., Schleimer R. P. Regulation of human basophil and lung mast cell function by cyclic adenosine monophosphate. J Immunol. 1988 Jan 15;140(2):571–579. [PubMed] [Google Scholar]
  10. Post M. J., te Biesebeek J. D., Wemer J., van Rooij H. H., Porsius A. J. Effects of milrinone, sulmazole and theophylline on adenosine enhancement of antigen-induced bronchoconstriction and mediator release in rat isolated lungs. Pulm Pharmacol. 1991;4(4):239–246. doi: 10.1016/0952-0600(91)90017-w. [DOI] [PubMed] [Google Scholar]
  11. Rossing T. H., Drazen J. M. Effects of milrinone on contractile responses of guinea pig trachea, lung parenchyma and pulmonary artery. J Pharmacol Exp Ther. 1986 Sep;238(3):874–879. [PubMed] [Google Scholar]
  12. Saito H., Hirai A., Tamura Y., Yoshida S. The 5-lipoxygenase products can modulate the synthesis of platelet-activating factor (alkyl-acetyl GPC) in Ca-ionophore A23187-stimulated rat peritoneal macrophages. Prostaglandins Leukot Med. 1985 Jun;18(3):271–286. doi: 10.1016/0262-1746(85)90059-9. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Sydbom A., Fredholm B. B. On the mechanism by which theophylline inhibits histamine release from rat mast cells. Acta Physiol Scand. 1982 Feb;114(2):243–251. doi: 10.1111/j.1748-1716.1982.tb06978.x. [DOI] [PubMed] [Google Scholar]
  15. Turner N. C., Dollery C. T. Release of arachidonic acid metabolites and histamine from sensitized guinea-pig lung following antigen challenge. Br J Pharmacol. 1988 Apr;93(4):751–758. doi: 10.1111/j.1476-5381.1988.tb11459.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Undem B. J., Peachell P. T., Lichtenstein L. M. Isoproterenol-induced inhibition of immunoglobulin E-mediated release of histamine and arachidonic acid metabolites from the human lung mast cell. J Pharmacol Exp Ther. 1988 Oct;247(1):209–217. [PubMed] [Google Scholar]
  17. Warner J. A., MacGlashan D. W., Jr, Peters S. P., Kagey-Sobotka A., Lichtenstein L. M. The pharmacologic modulation of mediator release from human basophils. J Allergy Clin Immunol. 1988 Sep;82(3 Pt 1):432–438. doi: 10.1016/0091-6749(88)90016-4. [DOI] [PubMed] [Google Scholar]
  18. Weishaar R. E., Burrows S. D., Kobylarz D. C., Quade M. M., Evans D. B. Multiple molecular forms of cyclic nucleotide phosphodiesterase in cardiac and smooth muscle and in platelets. Isolation, characterization, and effects of various reference phosphodiesterase inhibitors and cardiotonic agents. Biochem Pharmacol. 1986 Mar 1;35(5):787–800. doi: 10.1016/0006-2952(86)90247-9. [DOI] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES