Sensitizing effect of antimigraine drug sumatriptan on capsaicin-sensitive lung vagal neurons via 5-HT receptors and PKA: Relevance to adverse chest effects.

BackgroundThe antimigraine drug sumatriptan causes adverse chest effects, namely dyspnea and chest tightness, through unclear mechanisms. Dyspnea is an unpleasant sensation evoked by peripheral sensory signals transmitted to the central nervous system. Capsaicin-sensitive lung vagal (CSLV) afferents are nociceptive-like fibers that provide sensory input from the airways and lungs, mediating airway defense reflexes and evoking unpleasant respiratory sensations.

Stimulation of dorsal root ganglion with low-intensity focused ultrasound ameliorates pain responses through the GABA inhibitory pathway.

Aims: Chronic pain is a critical public health issue that severely impacts quality of life and poses significant treatment challenges, particularly due to the risk of adverse effects associated with pharmacological therapies. The search for effective non-invasive treatment alternatives has become increasingly relevant. Low-intensity focused ultrasound (LIFU) has been identified as an effective non-invasive strategy for pain management, although the underlying mechanism remains unclear.

The angiogenic role of the alpha 9-nicotinic acetylcholine receptor in triple-negative breast cancers.

Nicotine acts as an angiogenic factor by stimulating endogenous cholinergic pathways. Several subtypes of nicotinic acetylcholine receptors (nAChRs) have been demonstrated to be closely correlated to the formation and progression of different types of cancers. Recently, several studies have found that nicotinic acetylcholine receptors α9 (α9-nAChRs) are highly expressed in breast tumors, especially in tumors derived from patients diagnosed at advanced stages.

Release of ATP in the lung evoked by inhalation of irritant gases in rats.

Adenosine triphosphate (ATP) can be released into the extracellular milieu from various types of cells in response to a wide range of physical or chemical stresses. In the respiratory tract, extracellular ATP is recognized as an important signal molecule and trigger of airway inflammation. Chlorine (Cl), sulfur dioxide (SO), and ammonia (NH) are potent irritant gases and common industrial air pollutants due to their widespread uses as chemical agents.

Desmethylclomipramine triggers mitochondrial damage and death in TGF-β-induced mesenchymal type of A549 cells.

Lung cancer is the leading cause of cancer deaths, where the metastasis often causes chemodrug resistance and leads to recurrence after treatment. Desmethylclomipramine (DCMI), a bioactive metabolite of clomipramine, shows the therapeutic efficacy with antidepressive agency as well as potential cytostatic effects on lung cancer cells. Here, we demonstrated that DCMI effectively caused transforming growth factor (TGF)-β1-mediated mesenchymal type of A549 cells to undergo mitochondrial death via myeloid cell leukemia-1 (Mcl-1) suppression and activation of truncated Bid (tBid).

Endodontic Radiopacifying Application of Barium Titanate Prepared through a Combination of Mechanical Milling and Heat Treatment.

Mineral trioxide aggregates (MTA) are commonly used as endodontic filling materials but suffer from a long setting time and tooth discoloration. In the present study, the feasibility of using barium titanate (BTO) for discoloration and a calcium chloride (CaCl) solution to shorten the setting time was investigated. BTO powder was prepared using high-energy ball milling for 3 h, followed by sintering at 700-1300 °C for 2 h.

Premorbid use of selective beta-blockers improves sepsis incidence and course: Human cohort and animal model studies.

Introduction: Beta-blockers are widely prescribed to manage hypertension and cardiovascular diseases and have been suggested as an attractive therapy to improve the prognosis of sepsis. Herein, we investigated the potential benefits of premorbid selective beta-blocker use in sepsis with a real-world database and explored the underlying mechanism by and experiments.

Methods: A total of 64,070 sepsis patients and 64,070 matched controls who were prescribed at least one anti-hypertensive drug for more than 300 days within 1 year were selected for the nested case-control study.

Inhibitory effect of sulfur dioxide inhalation on Hering-Breuer inflation reflex in mice: role of voltage-gated potassium channels.

Slowly adapting receptors (SARs), vagal mechanosensitive receptors located in the lung, play an important role in regulating the breathing pattern and Hering-Breuer inflation reflex (HBIR). Inhalation of high concentration of sulfur dioxide (SO), a common environmental and occupational air pollutant, has been shown to selectively block the SAR activity in rabbits, but the mechanism underlying this inhibitory effect remained a mystery. We carried out this study to determine if inhalation of SO can inhibit the HBIR and change the eupneic breathing pattern, and to investigate further a possible involvement of voltage-gated K channels in the inhibitory effect of SO on these vagal reflex-mediated responses.

Mirabegron, a β3‑adrenoreceptor agonist, regulates right and left atrial arrhythmogenesis differently.

Mirabegron increases atrial fibrillation (AF) risk. The left atrium (LA) is the most critical 'substrate' for AF and has higher arrhythmogenesis compared with the right atrium (RA). The present study aimed to investigate the electrophysiological and arrhythmogenic effects of mirabegron on the LA and RA and clarify the potential underlying mechanisms.

Mechanisms Involved in the Stimulatory and Inhibitory Effects of 5-Hydroxytryptamine on Vagal Mechanosensitive Afferents in Rat Lung.

Mechanosensitive vagal afferents in the lung, rapidly and slowly adapting receptors (RARs and SARs, respectively), play an important role in eliciting the reflexes that regulate the normal airway function. A profound bronchoconstrictive effect of 5-hydroxytryptamine (5-HT) has been extensively reported in various animal species, but its influence on the SAR and RAR activity is not known. This study investigated the effect of 5-HT on these receptors, and the possible mechanisms involved.

Airway Exposure to 1,3-Beta-d-Glucan Induces Airway Hyperresponsiveness in Guinea Pigs.

1,3-Beta-d-glucan (β-glucan) is a component of mold cell walls and is frequently found in fungi and house dust mites. The studies of β-glucan are inconsistent, although it has been implicated in airway adverse responses. This study was carried out to determine whether airway hyperresponsiveness was seen 24 h after airway exposure to β-glucan in guinea pigs.

Efficacy and safety of anti-interleukin-5 therapy in patients with chronic obstructive pulmonary disease: A meta-analysis of randomized, controlled trials.

Background: Anti-interleukin-5 (IL-5) therapy has been proposed as a novel treatment option for patients with chronic obstructive pulmonary disease (COPD). However, its efficacy for preventing COPD exacerbation remains unclear.

Methods: A literature review was conducted to August 26th 2019.

Involvement of Capsaicin-Sensitive Lung Vagal Neurons and TRPA1 Receptors in Airway Hypersensitivity Induced by 1,3-β-D-Glucan in Anesthetized Rats.

Airway exposure to 1,3-β-D-glucan (β-glucan), an essential component of the cell wall of several pathogenic fungi, causes various adverse responses, such as pulmonary inflammation and airway hypersensitivity. The former response has been intensively investigated; however, the mechanism underlying β-glucan-induced airway hypersensitivity is unknown. Capsaicin-sensitive lung vagal (CSLV) afferents are very chemosensitive and stimulated by various insults to the lungs.

Hypersensitivity of Airway Reflexes Induced by Hydrogen Sulfide: Role of TRPA1 Receptors.

The activation of capsaicin-sensitive lung vagal (CSLV) afferents can elicit airway reflexes. Hypersensitivity of these afferents is known to contribute to the airway hypersensitivity during airway inflammation. Hydrogen sulfide (HS) has been suggested as a potential therapeutic agent for airway hypersensitivity diseases, such as asthma, because of its relaxing effect on airway smooth muscle and anti-inflammatory effect.

Atrial arrhythmogenesis in a rabbit model of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) increases the risk of atrial fibrillation (AF), however, its arrhythmogenic mechanisms are unclear. This study investigated the effects of COPD on AF triggers (pulmonary veins, PVs) and substrates (atria), and their potential underlying mechanisms. Electrocardiographic, echocardiographic, and biochemical studies were conducted in control rabbits and rabbits with human leukocyte elastase (0.

Mechanisms underlying the stimulatory effect of inhaled sulfur dioxide on vagal bronchopulmonary C-fibres.

Key Points: Brief inhalation of SO of concentration >500 p.p.m.

Stimulatory Effect of 5-Hydroxytryptamine (5-HT) on Rat Capsaicin-Sensitive Lung Vagal Sensory Neurons via Activation of 5-HT Receptors.

5-hydroxytryptamine (5-HT) is an inflammatory mediator known to be released in lung. Capsaicin-sensitive lung vagal (CSLV) afferents function as a primary sensor for detecting chemical stimuli and produce consequent reflexes during lung inflammation. To characterize the effect of 5-HT on CSLV afferents, responses of cardiorespiratory reflexes and single-unit C-fiber afferents to right-atrial injections of 5-HT were investigated in anesthetized Sprague-Dawley rats.

Immediate and delayed potentiating effects of tumor necrosis factor-α on TRPV1 sensitivity of rat vagal pulmonary sensory neurons.

We studied acute effects of tumor necrosis factor-α (TNFα) on the sensitivity of isolated rat vagal pulmonary sensory neurons. Our results showed the following. First, a brief pretreatment with a low dose of TNFα (1.

Interaction between TRPA1 and TRPV1: Synergy on pulmonary sensory nerves.

Transient receptor potential ankyrin type 1 (TRPA1) and vanilloid type 1 (TRPV1) receptors are co-expressed in vagal pulmonary C-fiber sensory nerves. Because both these ligand-gated non-selective cation channels are sensitive to a number of endogenous inflammatory mediators, it is highly probable that they can be activated simultaneously during airway inflammation. Studies were carried out to investigate whether there is an interaction between these two polymodal transducers upon simultaneous activation, and how it modulates the activity of vagal pulmonary C-fiber sensory nerves.

Airway extravasation induced by increasing airway temperature in ovalbumin-sensitized rats.

This study was carried out to determine whether hyperventilation of humidified warm air (HWA) induced airway extravasation in ovalbumin (Ova)-sensitized rats. Our results showed: (1) After isocapnic hyperventilation with HWA for 2 min, tracheal temperature (Ttr) was increased to 40.3°C, and the Evans blue contents in major airways and lung tissue were elevated to 651% and 707%, respectively, of that after hyperventilation with humidified room air in Ova-sensitized rats; this striking effect of HWA was absent in control rats.

Role of calcium ions in the positive interaction between TRPA1 and TRPV1 channels in bronchopulmonary sensory neurons.

Both transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are abundantly expressed in bronchopulmonary C-fiber sensory nerves and can be activated by a number of endogenous inflammatory mediators. A recent study has reported a synergistic effect of simultaneous TRPA1 and TRPV1 activations in vagal pulmonary C-fiber afferents in anesthetized rats, but its underlying mechanism was not known. This study aimed to characterize a possible interaction between these two TRP channels and to investigate the potential role of Ca(2+) as a mediator of this interaction in isolated rat vagal pulmonary sensory neurons.

Bronchoconstriction induced by increasing airway temperature in ovalbumin-sensitized rats: role of tachykinins.

This study was carried out to determine the effect of allergic inflammation on the airway response to increasing airway temperature. Our results showed the following: 1) In Brown-Norway rats actively sensitized by ovalbumin (Ova), isocapnic hyperventilation with humidified warm air (HWA) for 2 min raised tracheal temperature (Ttr) from 33.4 ± 0.

Hydrogen sulfide induces hypersensitivity of rat capsaicin-sensitive lung vagal neurons: role of TRPA1 receptors.

The sensitization of capsaicin-sensitive lung vagal (CSLV) afferents by inflammatory mediators is important in the development of airway hypersensitivity. Hydrogen sulfide (H2S) is an endogenous mediator inducing hyperalgesia through transient receptor potential ankyrin 1 (TRPA1) receptors located on nociceptors. We conducted this study to determine whether H2S elevates the sensitivity of rat CSLV afferents.