Dataset Information

Galactomannan and Zymosan Block the Epinephrine-Induced Particle Transport in Tracheal Epithelium.

ABSTRACT:

Background

Ciliary beating by respiratory epithelial cells continuously purges pathogens from the lower airways. Here we investigated the effect of the fungal cell wall polysaccharides Galactomannan (GM) and Zymosan (Zym) on the adrenergic activated particle transport velocity (PTV) of tracheal epithelium.

Methods

Experiments were performed using tracheae isolated from male C57BL/6J mice. Transport velocity of the cilia bearing epithelial cells was measured by analysing recorded image sequences. Generation of reactive oxygen species (ROS) were determined using Amplex Red reagents. PCR experiments were performed on isolated tracheal epithelium to identify adrenergic receptor mRNA.

Results

The adrenergic receptors ?1D, ?2A, ?1 and ?2 have been identified in isolated tracheal epithelium. We found epinephrine responsible for an increase in PTV, which could only be reduced by selective ?-receptor-inhibition. In addition, either GM or Zym prevented the epinephrine induced PTV increase. Furthermore, we observed a strong ROS generation evoked by GM or Zym. However, epinephrine induced increase in PTV recovered in the presence of GM and Zym after application of ROS scavengers.

Conclusion

Both GM or Zym trigger reversible ROS generation in tracheal tissue leading to inhibition of the ?-adrenergic increase in PTV.

SUBMITTER: Weiterer S

PROVIDER: S-EPMC4646458 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Galactomannan and Zymosan Block the Epinephrine-Induced Particle Transport in Tracheal Epithelium.

Weiterer Sebastian S Kohlen Thomas T Veit Florian F Sachs Lydia L Uhle Florian F Lichtenstern Christoph C Weigand Markus A MA Henrich Michael M

PloS one 20151116 11

<h4>Background</h4>Ciliary beating by respiratory epithelial cells continuously purges pathogens from the lower airways. Here we investigated the effect of the fungal cell wall polysaccharides Galactomannan (GM) and Zymosan (Zym) on the adrenergic activated particle transport velocity (PTV) of tracheal epithelium.<h4>Methods</h4>Experiments were performed using tracheae isolated from male C57BL/6J mice. Transport velocity of the cilia bearing epithelial cells was measured by analysing recorded i ...[more]

PMID: 26571499

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Project description:Background: Mucociliary clearance is a pivotal physiological mechanism that protects the lung by ridding the lower airways of pollution and colonization by pathogens, thereby preventing infections. The fixed 20:1 combination of cafedrine and theodrenaline has been used to treat perioperative hypotension or hypotensive states due to emergency situations since the 1960s. Because mucociliary clearance is impaired during mechanical ventilation and critical illness, the present study aimed to evaluate the influence of cafedrine/theodrenaline on mucociliary clearance. Material and Methods: The particle transport velocity (PTV) of murine trachea preparations was measured as a surrogate for mucociliary clearance under the influence of cafedrine/theodrenaline, cafedrine alone, and theodrenaline alone. Inhibitory substances were applied to elucidate relevant signal transduction cascades. Results: All three applications of the combination of cafedrine/theodrenaline, cafedrine alone, or theodrenaline alone induced a sharp increase in PTV in a concentration-dependent manner with median effective concentrations of 0.46 µM (consisting of 9.6 µM cafedrine and 0.46 µM theodrenaline), 408 and 4 μM, respectively. The signal transduction cascades were similar for the effects of both cafedrine and theodrenaline at the murine respiratory epithelium. While PTV remained at its baseline value after non-selective inhibition of β-adrenergic receptors and selective inhibition of β1 receptors, cafedrine/theodrenaline, cafedrine alone, or theodrenaline alone increased PTV despite the inhibition of the protein kinase A. However, IP3 receptor activation was found to be the pivotal mechanism leading to the increase in murine PTV, which was abolished when IP3 receptors were inhibited. Depleting intracellular calcium stores with caffeine confirmed calcium as another crucial messenger altering the PTV after the application of cafedrine/theodrenaline. Discussion: Cafedrine/theodrenaline, cafedrine alone, and theodrenaline alone exert their effects via IP3 receptor-associated calcium release that is ultimately triggered by β1-adrenergic receptor stimulation. Synergistic effects at the β1-adrenergic receptor are highly relevant to alter the PTV of the respiratory epithelium at clinically relevant concentrations. Further investigations are needed to assess the value of cafedrine/theodrenaline-mediated alterations in mucociliary function in clinical practice.

Project description:AimThe aim of this study was to evaluate the in vitro effect of coumarin and 15 monosubstituted derivatives on the inhibition of human platelet aggregation induced by various proaggregatory agonists, particularly by epinephrine.BackgroundThe emergence of residual platelet reactivity during the use of conventional antiplatelet agents (acetylsalicylic acid and clopidogrel) is one of the main causes of double therapy´s therapeutic failure. Platelet adrenoceptors participate in residual platelet reactivity. Therefore, it is necessary to develop new antiplatelet agents that inhibit epinephrine-induced platelet aggregation as a new therapeutic strategy. Information on the antiplatelet activity of coumarins in inhibiting epinephrine-induced aggregation is limited.ObjectiveThe objective of this study was to establish the structure-activity relationship (SAR) of coumarin derivatives with hydroxy, methoxy, and acetoxy groups in different positions of the coumarin nucleus to identify the most active molecules. Moreover, this study aimed to use in silico studies to suggest potential drug targets to which the molecules bind to produce antiplatelet effects.MethodsThe platelet aggregation was performed using a Lumi-aggregometer; the inhibitory activity of 16 compounds were evaluated by inducing the aggregation of human platelets (250 × 103/μl) with epinephrine (10 μM), collagen (2 μg/ml) or ADP (10 μM). The aggregation of control platelets was considered 100% of the response for each pro-aggregatory agonist.ResultsEleven molecules inhibited epinephrine-induced aggregation, with 3-acetoxycoumarin and 7-methoxycoumarin being the most active. Only coumarin inhibited collagen-induced platelet aggregation, but no molecule showed activity when using ADP as an inducer.ConclusionsIn silico studies suggest that most active molecules might have antagonistic interactions in the α2 and β2 adrenoceptors. The antiplatelet actions of these coumarins have the potential to reduce residual platelet reactivity and thus contribute to the development of future treatments for patients who do not respond adequately to conventional agents.

Dataset Information

Galactomannan and Zymosan Block the Epinephrine-Induced Particle Transport in Tracheal Epithelium.

Background

Methods

Results

Conclusion

Publications

Galactomannan and Zymosan Block the Epinephrine-Induced Particle Transport in Tracheal Epithelium.

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