Role of transient receptor potential and pannexin channels in cigarette smoke-triggered ATP release in the lung

Baxter, Matthew; Eltom, Suffwan; Dekkak, Bilel; Yew-Booth, Liang; Dubuis, Eric; Maher, Sarah A.; Belvisi, Maria G.; Birrell, Mark A.

doi:10.1136/thoraxjnl-2014-205467

Cited by 75 publications

(88 citation statements)

References 43 publications

(43 reference statements)

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“…Cigarette smoke exposure was found to cause a dose-related increase in ATP from primary human bronchial epithelial cells that was attenuated by blockers of TRPV1, TRPV4 and pannexin-1 channels (but not TRPA1) [99]. The same study documented an increase in TRPV4 mRNA expression in whole-lung tissue from COPD patients compared to healthy smokers and nonsmokers.…”

Section: Trpv4supporting

confidence: 56%

“…In the lung, TRPV1 expression has been found in human bronchial epithelial cells with an increase in expression in cells from the airways of patients with refractory asthma [99][100][101][102][103][104][105]109], fibroblasts [102], T-cells [106,107,115] and human alveolar macrophages [99]. Several studies suggest that TRPV1 channel activation evokes the release of proinflammatory cytokines and ATP from bronchial epithelial cells [99,[103][104][105]116]. Furthermore, in the context of COPD, the TRPV1 inhibitor JNJ17203212 reduced the cigarette smoke-induced release of ATP from human bronchial epithelial cells and TRPV1 −/− mice demonstrated less cigarette smoke-induced ATP release and exhibited reduced neutrophilic inflammation in the bronchoalveolar lavage fluid than wild-type mice [99].…”

Section: Trpv1mentioning

confidence: 99%

“…This effect is thought to be mediated by TRPV4-mediated ATP release from airway smooth muscle, which activates P2X4 receptors on mast cells to release cysteinyl leukotrienes (LT) which activate the Cys LT 1 receptor to evoke contraction [112,134]. Interestingly, many of the functional effects of TRPV4 activation are due to the release of ATP and activation of purinoceptors [8,82,99,134,135] and TRPV4-induced ATP release has been demonstrated in human macrophages, epithelial and smooth muscle cells [99,113,135]. In addition, TRPV4-induced ATP release has been shown to be released via a pannexin 1-dependent mechanism [82,99,135].…”

Section: Trpv4mentioning

confidence: 99%

“…Several studies suggest that TRPV1 channel activation evokes the release of proinflammatory cytokines and ATP from bronchial epithelial cells [99,[103][104][105]116]. Furthermore, in the context of COPD, the TRPV1 inhibitor JNJ17203212 reduced the cigarette smoke-induced release of ATP from human bronchial epithelial cells and TRPV1 −/− mice demonstrated less cigarette smoke-induced ATP release and exhibited reduced neutrophilic inflammation in the bronchoalveolar lavage fluid than wild-type mice [99]. Interestingly, in the same study TRPV1 mRNA expression was increased in whole-lung homogenates from emphysema patients compared to smokers and healthy nonsmokers, suggesting increased expression of TRPV1 associated with disease pathophysiology in non-neuronal cell types [99].…”

Section: Trpv1mentioning

confidence: 99%

“…TRPV4 is expressed across a wide range of non-neuronal human cell types in the airways, including structural cells such as airway smooth muscle, epithelial cells, fibroblasts and pulmonary vessels and inflammatory cells including macrophages (but not highly differentiated surrogates: the circulating monocytic precursor cell, monocyte derived macrophages, in vitro differentiated promonocytic THP-1 and U937 cells or promyelocytic HL-60 leukaemia cells), neutrophils and T-cells [99,107,111,112,114,[128][129][130][131][132]. However, in the respiratory system, the function of TRPV4 is probably best understood in relation to its role in acute lung injury, which is not covered in this review [133].…”

Section: Trpv4mentioning

confidence: 99%

See 4 more Smart Citations

The emerging role of transient receptor potential channels in chronic lung disease

Belvisi

Birrell

2017

Eur Respir J

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Chronic lung diseases such as asthma, chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis are a major and increasing global health burden with a high unmet need. Drug discovery efforts in this area have been largely disappointing and so new therapeutic targets are needed. Transient receptor potential ion channels are emerging as possible therapeutic targets, given their widespread expression in the lung, their role in the modulation of inflammatory and structural changes and in the production of respiratory symptoms, such as bronchospasm and cough, seen in chronic lung disease.

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Section: Trpv4supporting

confidence: 56%

Section: Trpv1mentioning

confidence: 99%

Section: Trpv4mentioning

confidence: 99%

Section: Trpv1mentioning

confidence: 99%

Section: Trpv4mentioning

confidence: 99%

See 3 more Smart Citations

The emerging role of transient receptor potential channels in chronic lung disease

Belvisi

Birrell

2017

Eur Respir J

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Mechanisms and Rationale for Targeted Therapies in Refractory and Unexplained Chronic Cough

Mazzone

McGarvey

2020

Clin Pharma and Therapeutics

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Chronic cough, defined as a cough lasting > 8 weeks, is a common medical condition that exerts a substantial physical, mental, and social burden on patients. A subset of patients with chronic cough are troubled with a cough that persists despite optimal treatment of presumed associated common and uncommon conditions (refractory chronic cough; RCC) or in which no diagnosable cause for cough can be identified despite extensive assessment (unexplained chronic cough; UCC). Many of these patients exhibit clinical features of cough hypersensitivity, including laryngeal paresthesia, hypertussia, and allotussia. Over-the-counter cough remedies are ineffective and can lead to intolerable side effects when used for RCC/UCC, and the lack of approved treatments indicated for these conditions reflects a major unmet need. An increased understanding of the anatomy and neurophysiology of protective and pathologic cough has fostered a robust clinical development pipeline of several targeted therapies for RCC/UCC. This manuscript reviews the mechanisms presumed to underly RCC/UCC together with the rationale and clinical evidence for several targeted therapies currently under clinical investigation, including transient receptor potential channel antagonists, P2X3-receptor antagonists, voltage-gated sodium channel blockers, neuromodulators, and neurokinin-1-receptor antagonists. Finally, we provide an overview of targets that have been investigated in preclinical models of cough and other airway diseases that may hold future promise for clinical studies in RCC/UCC. Development of targeted therapies with different sites of action may foster a precision medicine approach to treat this heterogeneous, underserved patient population.

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Pannexin hemichannels: A novel promising therapy target for oxidative stress related diseases

Chen

2017

Journal Cellular Physiology

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Pannexins, which contain three subtypes: pannexin-1, -2, and -3, are vertebrate glycoproteins that form non-junctional plasma membrane intracellular hemichannels via oligomerization. Oxidative stress refers to an imbalance of the generation and elimination of reactive oxygen species (ROS). Studies have shown that elevated ROS levels are pivotal in the development of a variety of diseases. Recent studies indicate that the occurrence of these oxidative stress related diseases is associated with pannexin hemichannels. It is also reported that pannexins regulate the production of ROS which in turn may increase the opening of pannexin hemichannels. In this paper, we review recent researches about the important role of pannexin hemichannels in oxidative stress related diseases. Thus, pannexin hemichannels, novel therapeutic targets, hold promise in managing oxidative stress related diseases such as the tumor, inflammatory bowel diseases (IBD), pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), cardiovascular disease, insulin resistance (IR), and neural degeneration diseases.

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Role of transient receptor potential and pannexin channels in cigarette smoke-triggered ATP release in the lung

Cited by 75 publications

References 43 publications

The emerging role of transient receptor potential channels in chronic lung disease

The emerging role of transient receptor potential channels in chronic lung disease

Mechanisms and Rationale for Targeted Therapies in Refractory and Unexplained Chronic Cough

Pannexin hemichannels: A novel promising therapy target for oxidative stress related diseases

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