Glucocorticoid decreases airway tone via a nongenomic pathway

Wang, Chen; Li, Yijia; Zheng, Yiqing; Feng, Bing; Liu, Yan; Cao, Ji-Min

doi:10.1016/j.resp.2012.05.008

Cited by 12 publications

(13 citation statements)

References 20 publications

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“…Among anti-asthmatic drugs, the combination of inhaled glucocorticoids and β-agonists is the most potent and effective medication for asthma control. This appreciated action is not only due to the complementary effects of these two agents on the pathogenesis of asthma, but also attributed to enhanced bronchodilatation via the permissive action as we showed recently [12] and studies from other groups [13,14]. …”

Section: Introductionsupporting

confidence: 60%

“…This oscillation of circulating cortisol correlates with nocturnal symptom of asthma, which can be recapitulated by the trachea model mentioned above [12]. Central and peripheral clock systems communicate with each other at multiple levels.…”

Section: Resultsmentioning

confidence: 92%

“…To delineate the molecular mechanism of permissive action with clinical relevance, we first adopted a well-established ex vivo model [12]. Histamine, an important mediator of bronchoconstriction in asthma, was used to constrict the guinea pig tracheal spiral.…”

Section: Resultsmentioning

confidence: 99%

“…To provide further evidence, experiments were performed with membrane-impermeable steroids, namely BSA-conjugated cortisol (BSA-cortisol). Recently, we noticed a concentration threshold, only above which cortisol could amplify the action of isoprenaline [12]. To see whether it was also applicable for BSA-cortisol, we set a concentration gradient (840, 1680 and 2520 ng/ml), a series of dosages equivalent to cortisol of 100, 200 and 300 ng/ml, respectively, as the chemical linker and linkage stoichiometry (1:25) were well-defined for this commercially available preparation.…”

Section: Resultsmentioning

confidence: 99%

“…As we have already probed the possible role of classical glucocorticoid receptor (GR) with the use of RU486 [12], a probable explanation for this observation could be that membrane “receptor” of cortisol was not the sole target for the permissive action. Even so, not all the cortisol molecules conjugated to BSA could exist in a suitable steric configuration to interact with its membrane target and then initiate downstream signaling.…”

Section: Resultsmentioning

confidence: 99%

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Extraneuronal Monoamine Transporter Mediates the Permissive Action of Cortisol in the Guinea Pig Trachea: Possible Involvement of Tracheal Chondrocytes

Wang

Qiu²,

Zheng³

et al. 2013

PLoS ONE

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Cortisol, a member of glucocorticoids, could potentiate the action of catecholamine by a non-genomic mechanism. Although this permissive effect has been well appreciated in the anti-asthmatic medication, the underlying signaling pathway has remained mysterious. Here, we show that extraneuronal monoamine transporter (EMT), a membraneous reuptake transporter for circulating catecholamine clearance, is the direct target of cortisol in its permissive effect. We found that BSA-conjugated cortisol, which functions as a cortisol but cannot penetrate cell membrane, enhanced the spasmolytic effect of β-adrenoceptor agonist (isoprenaline) in histamine-sensitized tracheal spirals of guinea pigs, and pharmacological inhibition of EMT with famotidine was powerful enough to imitate the permissive action of cortisol. To our surprise, EMT protein expression was high in the chondrocytes of tracheal cartilage, but was undetectable in tracheal smooth muscle cells. The functionality of EMT was further confirmed with measurement of catecholamine uptake by tracheal chondrocytes. Moreover, cortisol-initiated membrane signaling could activate protein kinase C (PKC), which phosphorylates EMT and induces its internalization via a lipid raft-dependent pathway. Both of the mechanisms slow down the reuptake process by chondrocytes, leading to extracellular catecholamine accumulation and results in a more profound adrenergic signaling activation in tracheal smooth muscle cells. Thus, an EMT-centered pathway was proposed to explain the permissive action of cortisol. Collectively, our results highlight the role of EMT in the crosstalk between glucocorticoid and catecholamine. EMT may represent a promising target for adrenergic signaling modulation.

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Section: Introductionsupporting

confidence: 60%

Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Extraneuronal Monoamine Transporter Mediates the Permissive Action of Cortisol in the Guinea Pig Trachea: Possible Involvement of Tracheal Chondrocytes

Wang

Qiu²,

Zheng³

et al. 2013

PLoS ONE

Self Cite

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Stress and tinnitus

Mazurek

Szczepek

Hébert

2015

HNO

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Emotional stress is a constant companion of tinnitus patients, since this phantom sound can unfortunately be a very effective stressor. However, the mechanism of stress contribution to the onset or progression of tinnitus remains unknown. Here, we review the pathways induced by emotional stress and the outcome of their induction: corticosteroid-dependent changes in gene expression, epigenetic modulations, and impact of stress on neuronal plasticity and neurotransmission. Using clinical examples, we demonstrate the presence of emotional stress among tinnitus patients and we present methods to measure the degree of stress. The evidence causally linking emotional stress with tinnitus is still indirect-the main difficulty lies in the inaccessibility of human auditory tissues and the inability to directly measure tinnitus-induced psychological distress in animal models. However, we believe that translational research is the future way of filling this gap, finding the answers, and thereby improving both the diagnosis and treatment of tinnitus patients.

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Steroids and antihistamines synergize to inhibit rat’s airway smooth muscle contractility

Liu

Chu

Kao

et al. 2014

Eur Arch Otorhinolaryngol

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Both glucocorticoids and H1-antihistamines were widely used on patients with allergic rhinitis (AR) and obstructive airway diseases. However, their direct effects on airway smooth muscle were not fully explored. In this study, we tested the effectiveness of prednisolone (Kidsolone) and levocetirizine (Xyzal) on isolated rat trachea submersed in Kreb's solution in a muscle bath. Changes in tracheal contractility in response to the application of parasympathetic mimetic agents were measured. The following assessments of the drug were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10(-6) M methacholine; (3) effect of the drug on electrical field stimulation (EFS) induced tracheal smooth muscle contractions. The result revealed sole use of Kidsolone or Xyzal elicited no significant effect or only a little relaxation response on tracheal tension after methacholine treatment. The tension was 90.5 ± 7.5 and 99.5 ± 0.8 % at 10(-4) M for Xyzal and 10(-5) M for Kidsolone, respectively. However, a dramatically spasmolytic effect was observed after co-administration of Kidsolone and Xyzal and the tension dropped to 67.5 ± 13.6 %, with statistical significance (p < 0.05). As for EFS-induced contractions, Kidsolone had no direct effect but Xyzal could inhibit it, with increasing basal tension. In conclusion, using glucocorticoids alone had no spasmolytic effect but they can be synergized with antihistamines to dramatically relax the trachea smooth muscle within minutes. Therefore, for AR patients with acute asthma attack, combined use of those two drugs is recommended.

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Glucocorticoid decreases airway tone via a nongenomic pathway

Cited by 12 publications

References 20 publications

Extraneuronal Monoamine Transporter Mediates the Permissive Action of Cortisol in the Guinea Pig Trachea: Possible Involvement of Tracheal Chondrocytes

Extraneuronal Monoamine Transporter Mediates the Permissive Action of Cortisol in the Guinea Pig Trachea: Possible Involvement of Tracheal Chondrocytes

Stress and tinnitus

Steroids and antihistamines synergize to inhibit rat’s airway smooth muscle contractility

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