Abstract
In anaesthetized guinea-pigs pretreated with propranolol (1 mg/kg, i.v.), platelet activating factor (Paf, 0.02 μg/kg, i.v.) caused an acute increase in airways response to histamine (0.5–3.0 μg/kg, i.v.) measured as intratracheal pressure. Treatment with the cyclooxygenase inhibitors, aspirin (10 mg/kg, i.v.) or indomethacin (5 mg/kg, i.v.), enhanced the magnitude and duration of this effect but a combined lipoxygenase/cyclooxygenase inhibitor, BW 755C (20 mg/kg, i.v.), prevented the increase in responsiveness. In aspirin treated animals, a putative lipoxygenase inhibitor NDGA (10 mg/kg, i.v.). or atropine methyl nitrate (1 mg/kg, i.v.) or bilateral vagotomy reduced the magnitude of Paf-induced increased histamine responses but did not prevent the effect.
Bronchoconstriction induced by Paf was variably influenced by the drug treatments. These data suggest that Paf causes an acute increase in airways responsiveness to histamine in the guinea-pig through a mechanism that may, in part, be dependant on the release of lipoxygenase metabolites.
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G. Camussi, I. Pawlowski, C. Tetta, C. Roffinello, M. Alberton, J. Brentjens and G. Andres,Acute lung inflammation induced in the rabbit by local instillation of 1-0-Octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine or of native platelet-activating factor, Am. J. Pathol.112, 78–88 (1983).
A. J. Wardlow and A. B. Kay,Paf-acether is a potent chemotactic for human eosinophils, J. All. Clin. Immunol.88, Suppl., 463 (1986).
K. F. Chung, H. Aizawa, G. D. Leikauf, J. F. Euki, T. W. Evans and J. A. Nadel,Airways hyperresponsiveness induced by platelet activating factor: role of thromboxane generation, J. Pharmacol. Expl. Therap.236, 580–584 (1986).
F. M. Cuss, C. M. Dixon and P. J. Barnes,Effects of inhaled platelet activating factor on pulmonary function and bronchial responsiveness in man. Lancetii, 189–192 (1986).
M. F. Fitzgerald, S. Moncada and L. Parente,The release of Paf-acether and lyso-Paf from sensitized guinea-pig lungs, Brit. J. Pharmacol. 86, 573P (1985).
T. Nakamura, Y. Morita, M. Kuriyama, K. Ishihara, K. Ito and T. Miyamoto,Platelet-activating factor in late asthmatic response. Int. Archs. Allergy Appl. Immunol.82, 57–61 (1987).
S. Desquand, C. Touvay, J. Randon, V. Lagente, B. Vilain, I. Maridonneau-Parini, A. Etienne, J. Lefort, P. Braqet and B. B. Vargaftig,Interference of BN52021 (Ginkolide B) with the bronchopulmonary effects of Paf-acether in the guineapig. Eur. J. Pharmacol.127, 83–95 (1986).
D. A. Handley, J. C. Tomesch and R. N. Saunders,Inhibition of PAF-induced systemic responses in the rat, guineapig, dog and primate by the receptor antagonist SRI 63441, Thrombosis Haemostasis56, 40 (1986).
L. Mazzoni, J. Morley, C. P. Page and S. Sanjar,Induction of airway hyper-reactivity by platelet activating factor in the guinea-pig, J. Physiol.365, 107P (1985).
L. Mazzoni, J. Morley, C. P. Page and S. Sanjar,Prophylactic anti-asthma drugs impair the airway hyper-reactivity that follows exposure to platelet activating factor (PAF), Brit. J. Pharmacol.86, 571P (1985).
M. W. McCulloch, C. Proctor and M. J. Rand,Evidence for an adrenergic homeostatic bronchodilator reflex mechanism, Eur. J. Pharmacol.2, 214–223 (1967).
N. F. Voelkel, S. Worthen, J. T. Reeves, P. M. Henson and R. C. Murphy,Non-immunological production of leukotrienes induced by platelet-activating factor, Science218, 286–288 (1982).
A. M. Lefer, D. M. Roth, D. J. Lefer and J. B. Smith,Potentiation of leukotriene formation in pulmonary and vascular tissue, Naunyn-Schmiedeberg's Arch. Pharmacol.326, 186–189 (1984).
A. G. Stewart, D. C. Thompson and M. R. Fennessy,Involvement of capsaicin-sensitive afferent neurones in a vagal dependent interaction between leukotriene D 4 and histamine on bronchomotor tone, Agents and Actions15, 500–508 (1984).
A. G. Stewart, D. C. Thompson and M. R. Fennessy,Aerosolized and intravenously administered leukotrienes: effects on the bronchoconstrictor potency of histamine in the guinea-pig. Brit. J. Pharmacol.87, 741–749 (1986).
N. P. Stimler-Gerard,Parasympathetic stimulation as a mechanism for platelet-activating factor-induced contractile responses in the lung, J. Pharmacol. Expt. Therap.237, 209–213 (1986).
R. Hamel, P. Masson, A. W. Ford-Hutchinson, T. R. Jones, G. Brunet and H. Piechuta,Differing mechanisms for leukotriene D 4 -induced bronchoconstriction in guinea-pigs following intravenous and aerosol administration, Prostaglandins24, 419–432 (1982).
R. M. McMillan, A. J. Millest, K. E. Proudman and K. B. Taylor,Evaluation of lipoxygenase inhibitors ex vivo, Brit. J Pharmacol.87, 53P (1986).
A. J. Lewis, A. Dervinis and J. Chang,The effects of antiallergic and bronchodilator drugs on platelet-activating factor (PAF-acether)-induced bronchospasm and platelet aggregation, Agents and Actions15, 636–642, (1987).
B. B. Vargaftig, J. Lefort, M. Chignard and J. Benveniste,Platelet activating factor induces a platelet dependent bronchoconstriction unrelated to the formation of prostaglandin derivatives, Eur. J. Pharmacol.65, 185–192 (1980).
M. O'Donnell, B. Yaremko, H. Crowley and A. F. Welton,Characterization of the biological effects of leukotriene E 4 (LTE) and platelet activating factor (PAF) in animal models. Fed. Proc42, 442 (1983).
J. Bonnet, D. Thibaudeau and P. Bessin,Dependency of the Paf-acether-induced bronchospasm on the lipoxygenase pathway in the guinea-pig, Prostaglandins26, 457–466 (1983).
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Anderson, G.P., White, H.L. & Fennessy, M.R. Increased airways responsiveness to histamine induced by platelet activating factor in the guinea-pig: possible role of lipoxygenase metabolites. Agents and Actions 24, 1–7 (1988). https://doi.org/10.1007/BF01968073
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DOI: https://doi.org/10.1007/BF01968073