Platelet activating factor and tracheobronchial respiratory glycoconjugate release in feline and human explants: involvement of the lipoxygenase pathway

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J D LundgrenJ H Shelhamer

Abstract

It has been suggested that platelet activating factor (PAF) may participate in many aspects of bronchial asthma, including stimulation of mucus secretion. Feline tracheal and human bronchial explant production of respiratory glycoconjugates (RGC) in response to platelet activating factor (PAF) was investigated, in order to differentiate the actions of this putative mediator on mucus secretion. PAF caused a dose-dependent increase in RGC release in concentrations ranging from 100-0.5 microM during a 1-2 hours incubation with either feline or human explants, and the effect was inhibited by the PAF receptor antagonists Ro 19-3704. Several lines of evidence suggest that PAF enhances RGC release indirectly through stimulation of the production of lipoxygenase metabolites of arachidonic acid. 1) Incubation of 10 microM PAF together with arachidonic acid (100 micrograms/ml) enhances PAF's stimulatory effect on RGC release in cats. 2) The cyclooxygenase inhibitor ibuprofen (65 and 420 microM) either failed to effect or slightly enhanced PAF induced RGC release in both species. 3) The combined cyclooxygenase and lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) as well as the putatively specific 5-lipoxygenase inhibitor L-651,392 ...Continue Reading

References

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Citations

Feb 1, 1992·American Journal of Respiratory Cell and Molecular Biology·R D RievesJ H Shelhamer
Feb 22, 2008·Journal of Occupational Medicine and Toxicology·Rene SchmidtUlrich Wagner
May 1, 1992·Experimental Lung Research·L A Cohn, K B Adler
Jul 11, 2003·Chest·Chikako KishiokaBruce K Rubin
Mar 5, 2003·Pharmacological Reviews·Charles BrinkTakehiko Yokomizo
Sep 4, 2015·Physiological Reviews·Jonathan H Widdicombe, Jeffrey J Wine
Mar 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·W R HendersonE Y Chi
Feb 13, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·M KomoriN Hara
Jun 1, 1992·Pulmonary Pharmacology·J D Lundgren, J N Baraniuk

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