Acrolein relaxes mouse isolated tracheal smooth muscle via a TRPA1-dependent mechanism

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    Abstract

    Airway sensory C-fibres express TRPA1 channels which have recently been identified as a key chemosensory receptor for acrolein, a toxic and highly prevalent component of smoke. TRPA1 likely plays an intermediary role in eliciting a range of effects induced by acrolein including cough and neurogenic inflammation. Currently, it is not known whether acrolein-induced activation of TRPA1 produces other airway effects including relaxation of mouse airway smooth muscle. The aims of this study were to examine the effects of acrolein on airway smooth muscle tone in mouse isolated trachea, and to characterise the cellular and molecular mechanisms underpinning the effects of acrolein. Isometric tension recording studies were conducted on mouse isolated tracheal segments to characterise acrolein-induced relaxation responses. Release of the relaxant PGE2 was measured by EIA to examine its role in the response. Use of selective antagonists/inhibitors permitted pharmacological characterisation of the molecular and cellular mechanisms underlying this relaxation response. Acrolein induced dose-dependent relaxation responses in mouse isolated tracheal segments. Importantly, these relaxation responses were significantly inhibited by the TRPA1 antagonists AP-18 and HC-030031, an NK1 receptor antagonist RP-67580, and the EP2 receptor antagonist PF-04418948, whilst completely abolished by the non-selective COX inhibitor indomethacin. Acrolein also caused rapid PGE2 release which was suppressed by HC-030031. In summary, acrolein induced a novel bronchodilator response in mouse airways. Pharmacologic studies indicate that acrolein-induced relaxation likely involves interplay between TRPA1-expressing airway sensory C-fibres, NK 1 receptor-expressing epithelial cells, and EP2-receptor expressing airway smooth muscle cells. © 2014 Elsevier Inc.
    Original languageEnglish
    Pages (from-to)148-156
    JournalBiochemical Pharmacology
    Volume89
    Issue number1
    Early online date19 Feb 2014
    DOIs
    Publication statusPublished - 1 May 2014

    Fingerprint

    Acrolein
    Smooth Muscle
    Muscle
    Unmyelinated Nerve Fibers
    Dinoprostone
    Neurogenic Inflammation
    Neurokinin-1 Receptors
    Fibers
    Poisons
    Bronchodilator Agents
    Trachea
    Cough
    Smoke
    Indomethacin
    Smooth Muscle Myocytes
    Epithelial Cells
    Chemical activation
    Cells
    Pharmacology

    Cite this

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    title = "Acrolein relaxes mouse isolated tracheal smooth muscle via a TRPA1-dependent mechanism",
    abstract = "Airway sensory C-fibres express TRPA1 channels which have recently been identified as a key chemosensory receptor for acrolein, a toxic and highly prevalent component of smoke. TRPA1 likely plays an intermediary role in eliciting a range of effects induced by acrolein including cough and neurogenic inflammation. Currently, it is not known whether acrolein-induced activation of TRPA1 produces other airway effects including relaxation of mouse airway smooth muscle. The aims of this study were to examine the effects of acrolein on airway smooth muscle tone in mouse isolated trachea, and to characterise the cellular and molecular mechanisms underpinning the effects of acrolein. Isometric tension recording studies were conducted on mouse isolated tracheal segments to characterise acrolein-induced relaxation responses. Release of the relaxant PGE2 was measured by EIA to examine its role in the response. Use of selective antagonists/inhibitors permitted pharmacological characterisation of the molecular and cellular mechanisms underlying this relaxation response. Acrolein induced dose-dependent relaxation responses in mouse isolated tracheal segments. Importantly, these relaxation responses were significantly inhibited by the TRPA1 antagonists AP-18 and HC-030031, an NK1 receptor antagonist RP-67580, and the EP2 receptor antagonist PF-04418948, whilst completely abolished by the non-selective COX inhibitor indomethacin. Acrolein also caused rapid PGE2 release which was suppressed by HC-030031. In summary, acrolein induced a novel bronchodilator response in mouse airways. Pharmacologic studies indicate that acrolein-induced relaxation likely involves interplay between TRPA1-expressing airway sensory C-fibres, NK 1 receptor-expressing epithelial cells, and EP2-receptor expressing airway smooth muscle cells. {\circledC} 2014 Elsevier Inc.",
    author = "Esther Cheah and Philip Burcham and Tracy Mann and Peter Henry",
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    Acrolein relaxes mouse isolated tracheal smooth muscle via a TRPA1-dependent mechanism. / Cheah, Esther; Burcham, Philip; Mann, Tracy; Henry, Peter.

    In: Biochemical Pharmacology, Vol. 89, No. 1, 01.05.2014, p. 148-156.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Acrolein relaxes mouse isolated tracheal smooth muscle via a TRPA1-dependent mechanism

    AU - Cheah, Esther

    AU - Burcham, Philip

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    AB - Airway sensory C-fibres express TRPA1 channels which have recently been identified as a key chemosensory receptor for acrolein, a toxic and highly prevalent component of smoke. TRPA1 likely plays an intermediary role in eliciting a range of effects induced by acrolein including cough and neurogenic inflammation. Currently, it is not known whether acrolein-induced activation of TRPA1 produces other airway effects including relaxation of mouse airway smooth muscle. The aims of this study were to examine the effects of acrolein on airway smooth muscle tone in mouse isolated trachea, and to characterise the cellular and molecular mechanisms underpinning the effects of acrolein. Isometric tension recording studies were conducted on mouse isolated tracheal segments to characterise acrolein-induced relaxation responses. Release of the relaxant PGE2 was measured by EIA to examine its role in the response. Use of selective antagonists/inhibitors permitted pharmacological characterisation of the molecular and cellular mechanisms underlying this relaxation response. Acrolein induced dose-dependent relaxation responses in mouse isolated tracheal segments. Importantly, these relaxation responses were significantly inhibited by the TRPA1 antagonists AP-18 and HC-030031, an NK1 receptor antagonist RP-67580, and the EP2 receptor antagonist PF-04418948, whilst completely abolished by the non-selective COX inhibitor indomethacin. Acrolein also caused rapid PGE2 release which was suppressed by HC-030031. In summary, acrolein induced a novel bronchodilator response in mouse airways. Pharmacologic studies indicate that acrolein-induced relaxation likely involves interplay between TRPA1-expressing airway sensory C-fibres, NK 1 receptor-expressing epithelial cells, and EP2-receptor expressing airway smooth muscle cells. © 2014 Elsevier Inc.

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