抗趋化因子口服药物XC8对TRPA1而非TRPV1通道激动剂引发的豚鼠咳嗽的影响

IF 2.3 Q2 RESPIRATORY SYSTEM

Pulmonary Therapy Pub Date : 2022-03-01 Epub Date: 2022-02-08 DOI:10.1007/s41030-022-00183-y

Julia Romanova, Anastasia Rydlovskaya, Stepan Mochalov, Oxana Proskurina, Yulia Gorokh, Vladimir Nebolsin

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引用次数: 3

摘要

慢性咳嗽严重影响患者的生活质量，目前尚无有效的许可治疗方法。咳嗽是严重急性呼吸综合征相关冠状病毒2 (SARS-CoV-2)感染、哮喘和其他疾病的并发症。不同疾病的患者对不同的咳嗽诱因有不同的咳嗽反应，从而提示神经元功能障碍的各种机制。之前，我们证明了小分子药物XC8具有临床抗哮喘作用。本研究的目的是探讨XC8对咳嗽的影响。方法:研究XC8对激活人瞬时受体电位(TRP)阳离子通道TRPA1或TRPV1的激动剂致豚鼠咳嗽的止咳作用。我们通过荧光成像平板阅读器(FLIPR)检测了XC8对人阳离子通道TRPA1、TRPV1、TRPM8、P2X嘌呤受体2 (P2X2)和人酸感应离子通道3 (hASIC3)的拮抗活性。结果:XC8在柠檬酸单独(高达67.1%)或与IFN-γ联合(高达76.4%)诱导的豚鼠中表现出明显的止咳活性和剂量依赖性抑制咳嗽。XC8抑制由反复吸入柠檬酸(高达80%)或肉桂醛(高达60%)引起的咳嗽反射。XC8对辣椒素引起的咳嗽无抑制作用。未检测到XC8对人TRPA1、TRPV1、TRPM8、P2X2或hASIC3的直接激动/拮抗活性。结论:XC8对TRPA1(柠檬酸/肉桂醛)通道激活引起的咳嗽有抑制作用，而对TRPV1(辣椒素)通道无抑制作用。XC8抑制咳嗽反射，抑制IFN-γ对咳嗽的增强作用。XC8可能对慢性咳嗽伴炎症患者具有重要的治疗价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

The Effect of Anti-Chemokine Oral Drug XC8 on Cough Triggered by The Agonists of TRPA1 But Not TRPV1 Channels in Guinea Pigs.

查看原文本刊更多论文

The Effect of Anti-Chemokine Oral Drug XC8 on Cough Triggered by The Agonists of TRPA1 But Not TRPV1 Channels in Guinea Pigs.

Introduction: Chronic cough heavily affects patients' quality of life, and there are no effective licensed therapies available. Cough is a complication of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection, asthma, and other diseases. Patients with various diseases have a different profile of tussive responses to diverse cough triggers, thereby suggesting sundry mechanisms of neuronal dysfunctions. Previously, we demonstrated that the small molecule drug XC8 shows a clinical anti-asthmatic effect. The objective of the present study was to investigate the effect of XC8 on cough.

Methods: We studied the antitussive effect of XC8 on cough induced by agonists activating human transient receptor potential (TRP) cation channels TRPA1 or TRPV1 in guinea pigs. We checked the agonistic/antagonistic activity of XC8 on the human cation channels TRPA1, TRPV1, TRPM8, P2X purinoceptor 2 (P2X2), and human acid sensing ion channel 3 (hASIC3) in Fluorescent Imaging Plate Reader (FLIPR) assay.

Results: XC8 demonstrated clear antitussive activity and dose-dependently inhibited cough in guinea pigs induced by citric acid alone (up to 67.1%) or in combination with IFN-γ (up to 76.4%). XC8 suppressed cough reflexes induced by the repeated inhalation of citric acid (up to 80%) or by cinnamaldehyde (up to 60%). No activity of XC8 against cough evoked by capsaicin was revealed. No direct agonistic/antagonistic activity of XC8 on human TRPA1, TRPV1, TRPM8, P2X2, or hASIC3 was detected.

Conclusions: XC8 acts against cough evoked by the activation of TRPA1 (citric acid/cinnamaldehyde) but not TRPV1 (capsaicin) channels. XC8 inhibits the cough reflex and suppresses the cough potentiation by IFN-γ. XC8 might be of significant therapeutic value for patients suffering from chronic cough associated with inflammation.

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来源期刊

Pulmonary Therapy Medicine-Pulmonary and Respiratory Medicine

CiteScore

5.20

自引率

3.30%

发文量

审稿时长

6 weeks

期刊介绍： Aims and Scope Pulmonary Therapy is an international, open access, peer-reviewed (single-blind), and rapid publication journal. The scope of the journal is broad and will consider all scientifically sound research from pre-clinical, clinical (all phases), observational, real-world, and health outcomes research around the use of pulmonary therapies, devices, and surgical techniques. Areas of focus include, but are not limited to: asthma; chronic obstructive pulmonary disease; idiopathic pulmonary fibrosis; pulmonary hypertension; cystic fibrosis; lung cancer; respiratory tract disorders; allergic rhinitis and other respiratory allergies; influenza, pneumococcal infection, respiratory syncytial virus and other respiratory infections; and inhalers and other device therapies. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/series, trial protocols and short communications such as commentaries and editorials. Pulmonary Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. Rapid Publication The journal’s publication timelines aim for a rapid peer review of 2 weeks. If an article is accepted it will be published 3–4 weeks from acceptance. The rapid timelines are achieved through the combination of a dedicated in-house editorial team, who manage article workflow, and an extensive Editorial and Advisory Board who assist with peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid, efficient communication of the latest research and reviews, fostering the advancement of pulmonary therapies. Open Access All articles published by Pulmonary Therapy are open access. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning authors will always have an editorial contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE, GPP and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. Digital Features and Plain Language Summaries Pulmonary Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’. For examples of digital features please visit our showcase page https://springerhealthcare.com/expertise/publishing-digital-features/ Publication Fees Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of €4500/ $5100/ £3650. The journal will consider fee discounts and waivers for developing countries and this is decided on a case by case basis. Peer Review Process Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria. At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials, and Letters which are generally reviewed by one member of the Editorial Board. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case-by-case basis and should be sent to the journal editor. Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors’ or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. 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