Transient Receptor Potential (TRP) Channels in Airway Toxicity and Disease: An Update

Müller, Wernér E.G.; Alt, Philipp; Rajan, Suhasini; Schaller, Lena; Geiger, Fabienne; Dietrich, Alexander

doi:10.3390/cells11182907

Cited by 17 publications

(7 citation statements)

References 176 publications

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“…In the respiratory tract, a series of ion channels are expressed in airway cells and control the balance of intracellular Ca 2+ and extracellular Ca 2+ concentrations. Abnormal ion channel switching ultimately activates the pathogenesis of asthma (Valverde et al 2011 ; Muller, et al 2022 ). The exploration of participating ion channels revealed that L-VDLCCs, NSCCs, NCXs and potassium channels were regulated and that the channel currents were altered during the process of PP121-induced relaxation.…”

Section: Discussionmentioning

confidence: 99%

PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model

Li,

Xue,

Peng

et al. 2023

Mol Med

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Background Tyrosine kinase and phosphoinositide kinase pathways play important roles in asthma formation. As a dual tyrosine and phosphoinositide kinase inhibitor, PP121 has shown anticancer efficacy in multiple tumors. However, the study of PP121 in pulmonary diseases is still limited. Herein, we investigated the therapeutic activities of PP121 in asthma treatment. Methods Tension measurements and patch clamp recordings were made to investigate the anticontractile characteristics of PP121 in vitro. Then, an asthma mouse model was established to further explore the therapeutic characteristics of PP121 via measurement of respiratory system resistance, histological analysis and western blotting. Results We discovered that PP121 could relax precontracted mouse tracheal rings (mTRs) by blocking certain ion channels, including L-type voltage-dependent Ca2+ channels (L-VDCCs), nonselective cation channels (NSCCs), transient receptor potential channels (TRPCs), Na+/Ca2+ exchangers (NCXs) and K+ channels, and accelerating calcium mobilization. Furthermore, PP121 relieved asthmatic pathological features, including airway hyperresponsiveness, systematic inflammation and mucus secretion, via downregulation of inflammatory factors, mucins and the mitogen-activated protein kinase (MAPK)/Akt signaling pathway in asthmatic mice. Conclusion In summary, PP121 exerts dual anti-contractile and anti-inflammatory effects in asthma treatment, which suggests that PP121 might be a promising therapeutic compound and shed new light on asthma therapy.

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Section: Discussionmentioning

confidence: 99%

PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model

Li,

Xue,

Peng

et al. 2023

Mol Med

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“…In preclinical studies involving respiratory disease models, GDC-0334 exhibited inhibition toward edema formation, smooth muscle hyperreactivity, and cough response. 72 , 73 Drug discovery strategies have been challenged owing to the limited bioavailability of TRPA1 antagonists.…”

Section: Trpa1 As a Drug Targetmentioning

confidence: 99%

A Comprehensive Review on the Regulatory Action of TRP Channels: A Potential Therapeutic Target for Nociceptive Pain

Anand,

Rajagopal

2023

J Exp Neurosci

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The transient receptor potential (TRP) superfamily of ion channels in humans comprises voltage-gated, non-selective cation channels expressed both in excitable as well as non-excitable cells. Four TRP channel subunits associate to create functional homo- or heterotetramers that allow the influx of calcium, sodium, and/or potassium. These channels are highly abundant in the brain and kidney and are important mediators of diverse biological functions including thermosensation, vascular tone, flow sensing in the kidney and irritant stimuli sensing. Inherited or acquired dysfunction of TRP channels influences cellular functions and signaling pathways resulting in multifaceted disorders affecting skeletal, renal, cardiovascular, and nervous systems. Studies have demonstrated the involvement of these channels in the generation and transduction of pain. Based on the multifaceted role orchestrated by these TRP channels, modulation of the activity of these channels presents an important strategy to influence cellular function by regulating intracellular calcium levels as well as membrane excitability. Therefore, there has been a remarkable pharmaceutical inclination toward TRP channels as therapeutic interventions. Several candidate drugs influencing the activity of these channels are already in the clinical trials pipeline. The present review encompasses the current understanding of TRP channels and TRP modulators in pain and pain management.

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“…Transient receptor potential channels are non-selective Ca +2 channels involved in a plethora of pathological and physiological roles [ 17 , 18 , 19 , 20 , 21 ]. First described in Drosophila melanogaster (for review see: [ 22 , 23 , 24 ]), it is now known that their expressions and activation profiles on neuronal and non-neuronal cells can influence the protection against or the development of a range of chronic diseases in mammals, including pain [ 25 , 26 ], cardiovascular diseases [ 27 , 28 ], asthma [ 29 , 30 ], amongst others. Also, their contributions to MS have been explored within the last several decades, especially in regard to TRP vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) channels [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Effect of the TRPC4/TRPC5 Blocker, ML204, in Sucrose-Induced Metabolic Imbalance

Araújo¹,

Soczek

Pontes

et al. 2023

Pharmaceuticals

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Sugar-induced metabolic imbalances are a major health problem since an excessive consumption of saccharides has been linked to greater obesity rates at a global level. Sucrose, a disaccharide composed of 50% glucose and 50% fructose, is commonly used in the food industry and found in a range of fast, restaurant, and processed foods. Herein, we investigated the effects of a TRPC4/TRPC5 blocker, ML204, in the metabolic imbalances triggered by early exposure to sucrose-enriched diet in mice. TRPC4 and TRPC5 belong to the family of non-selective Ca+2 channels known as transient receptor potential channels. High-sucrose (HS)-fed animals with hyperglycaemia and dyslipidaemia, were accompanied by increased body mass index. mesenteric adipose tissue accumulation with larger diameter cells and hepatic steatosis in comparison to those fed normal diet. HS mice also exhibited enhanced adipose, liver, and pancreas TNFα and VEGF levels. ML204 exacerbated hyperglycaemia, dyslipidaemia, fat tissue deposition, hepatic steatosis, and adipose tissue and liver TNFα in HS-fed mice. Normal mice treated with the blocker had greater hepatic steatosis and adipose tissue cell numbers/diameter than those receiving vehicle, but showed no significant changes in tissue inflammation, glucose, and lipid levels. The results indicate that TRPC4/TRPC5 protect against the metabolic imbalances caused by HS ingestion.

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Transient Receptor Potential (TRP) Channels in Airway Toxicity and Disease: An Update

Cited by 17 publications

References 176 publications

PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model

PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model

A Comprehensive Review on the Regulatory Action of TRP Channels: A Potential Therapeutic Target for Nociceptive Pain

Analysis of the Effect of the TRPC4/TRPC5 Blocker, ML204, in Sucrose-Induced Metabolic Imbalance

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