Abstract
Allergic squirrel monkeys when exposed to an aerosol ofAscaris suum either develop a reproducible, immediate bronchoconstriction or an immediate bronchoconstriction followed by a reproducible late response. Pretreatment of ascaris-challenged squirrel monkeys with a potent, selective, orally active 5-lipoxygenase inhibitor, L-651,392 (4-bromo-2,7-dimethoxy-3,4-phenothizin-3-one), at a dose of 5 mg/kg p.o. resulted in near complete inhibition of the increases in pulmonary resistance (R L) and decreases in dynamic compliance (Cdyn) normally observed following exposure to the antigen. A lower dose (1 mg/kg p.o.) of L-651-392 produced only a significant inhibition of the decreases in Cdyn. In monkeys known to develop dual responses to antigen, L-651,392 (5 mg/kg p.o.) significantly attenuated the immediate response and markedly inhibited the late response. These results suggest an important role for leukotrienes in primary and late phase allergen-induced bronchoconstriction.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
C. S. McFarlane, H. Piechuta, R. A. Hall and A. W. Ford-Hutchinson,Effects of a contractile prostaglandin antagonist (L-640,035) upon allergen-induced bronchoconstriction in hyperreactive rats and conscious squirrel monkeys. Prostaglandins28, 173–182 (1984).
R. Hamel, C. S. McFarlane and A. W. Ford-Hutchinson,Late pulmonary responses induced by Ascaris allergen in conscious squirrel monkeys. J. Appl. Physiol.61, 2081–2087 (1986).
P. J. Piper,Formation and actions of leukotrienes. Physiol. Rev.64, 744–761 (1984).
Y. Guindon, Y. Girard, A. Maycock, A. W. Ford-Hutchinson, J. G. Atkinson, P. C. Bélanger, A. Dallob, D. DeSousa, H. Dougherty, R. Egan, M. M. Goldenberg, E. Ham, R. Fortin, P. Hamel, R. Hamel, C. K. Lau, Y. Leblanc, C. S. McFarlane, H. Piechuta, M. Thérien, c. Yoakim and J. Rokach,L-651,392: a novel, potent and selective 5-lipoxygenase inhibitor. In:Advances in Protaglandin Thromboxane and Leukotriene Research. Vol. 17, pp. 554–557 (Eds. B. Samuelsson, R. Paoletti and P. W. Ramwell). Raven Press, New York 1987.
H. Piechuta, A. W. Ford-Hutchinson and L. G. Letts,Inhibition of allergen-induced bronchoconstriction in hyperreactive rats as a model for testing 5-lipoxygenase inhibitors and leukotriene D 4 receptor antagonists. Agents and Actions, in press.
A. W. Ford-Hutchinson, R. Hamel and C. S. McFarlane,Pulmonary responses to exogenous leukotrienes. InLeukotrienes in Cardiovascular and Pulmonary Function. pp. 199–207 (Eds. A. Lefer and M. Gee). Alan Liss Press, New York 1985.
T. Ishizaka, K. Ishizaka, R. P. Orange and K. F. Austen,Pharmacological inhibition of the antigen-induced release of histamine and slow reacting substance of anaphylaxis (SRSA) from monkey lung tissues mediated by human IgE. J. Immunol.106, 1267–1271 (1971).
R. Patterson, and K. E. Harris,Inhibition of immunoglobulin E-mediated antigen-induced monkey asthma and skin reactions by 5, 8, 11, 14-eicosatetraymoic acid. J. Allergy Clin. Immunol.67, 146–152 (1981).
L. G. Letts, C. McFarlane, H. Piechuta and A. W. Ford-Hutchinson,The effects of 5-lipoxygenase inhibitor (L-651,392) and leukotriene D 4 antagonist (L-649,923) in two animal models of immediate hypersensitivity reactions. InAdvances in Prostaglandin, Thromboxane and Leukotriene Research. Vol. 17, pp. 1003–1007 (Eds. B. Samuelsson, R. Paoletti and P. W. Ramwell). Raven Press, New York 1987.
J. Pepys, F. E. Hargreave, M. Chan and D. S. McCarthy,Inhibitory effects of disodium cromoglycate on allergeninhalation tests. Lancet2, 134–137 (1968).
J. Pepys, and B. J. Hutchcroft,Bronchial provocation tests in etiologic diagnosis and analysis of asthma. Am. Rev. Respir. Dis.112, 829–859 (1975).
O. Cromwell, R. J. Shaw, S. R. Durham and A. B. Kay,Plasma LTB 4 concentrations during early and late phase antigen-induced asthmatic reactions. J. Allergy Clin. Immunol.73, 174 (1984).
L. Nagy, T. H. Lee and A. B. Kay,Neutrophil chemotactic activity in antigen-induced late asthmatic reactions. N. Engl. J. Med.306, 497–501 (1982).
E. G. Shephard, L. Malan, C. M. McFarlane, W. Mouton and J. R. Joubert,Lung function and plasma levels of thromboxane B 2,6-ketoprostaglandin F 1α and β-thromboglobulin in antigen-induced asthma before and after indomethacin pretreatment. Br. J. Clin. Pharmacol.19, 459–470 (1985).
W. M. Abraham, E. Russi, A. Wanner, J. C. Delehunt, L. D. Yerger and G. A. Chapman,Production of early and late pulmonary responses with inhaled leukotriene D 4 in allergic sheep. Prostaglandins29, 715–726 (1985).
W. M. Abraham, A. Wanner, J. S. Stevenson and G. A. Chapman,The effect of an orally active leukotriene D 4/E 4 antagonist, LY171883, on antigen-induced airway responses in allergic sheep. Prostaglandins31, 457–461 (1986).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
McFarlane, C.S., Hamel, R. & Ford-Hutchinson, A.W. Effects of a 5-lipoxygenase inhibitior (L-651,392) on primary and late pulmonary responses to ascaris antigen in the squirrel monkey. Agents and Actions 22, 63–68 (1987). https://doi.org/10.1007/BF01968818
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01968818