scholarly journals TRP Channels as Molecular Targets to Relieve Cancer Pain

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 1
Author(s):  
Milena Duitama ◽  
Yurany Moreno ◽  
Sandra Paola Santander ◽  
Zulma Casas ◽  
Jhon Jairo Sutachan ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Peripheral Sensitization ◽  
Sensory Stimuli ◽  
Patients With Cancer ◽  
Intracellular Signaling Pathways ◽  
Transient Receptor

Transient receptor potential (TRP) channels are critical receptors in the transduction of nociceptive stimuli. The microenvironment of diverse types of cancer releases substances, including growth factors, neurotransmitters, and inflammatory mediators, which modulate the activity of TRPs through the regulation of intracellular signaling pathways. The modulation of TRP channels is associated with the peripheral sensitization observed in patients with cancer, which results in mild noxious sensory stimuli being perceived as hyperalgesia and allodynia. Secondary metabolites derived from plant extracts can induce the activation, blocking, and desensitization of TRP channels. Thus, these compounds could act as potential therapeutic agents, as their antinociceptive properties could be beneficial in relieving cancer-derived pain. In this review, we will summarize the role of TRPV1 and TRPA1 in pain associated with cancer and discuss molecules that have been reported to modulate these channels, focusing particularly on the mechanisms of channel activation associated with molecules released in the tumor microenvironment.

scholarly journals Taste the Pain: The Role of TRP Channels in Pain and Taste Perception

2020 ◽  
Vol 21 (16) ◽  
pp. 5929 ◽  
Author(s):  
Edwin Aroke ◽  
Keesha Powell-Roach ◽  
Rosario Jaime-Lara ◽  
Markos Tesfaye ◽  
Abhrarup Roy ◽  
...  
Keyword(s):  
Pain Perception ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Taste Perception ◽  
Therapeutic Interventions ◽  
Sensory Stimuli ◽  
Transient Receptor ◽  
Trp Genes

Transient receptor potential (TRP) channels are a superfamily of cation transmembrane proteins that are expressed in many tissues and respond to many sensory stimuli. TRP channels play a role in sensory signaling for taste, thermosensation, mechanosensation, and nociception. Activation of TRP channels (e.g., TRPM5) in taste receptors by food/chemicals (e.g., capsaicin) is essential in the acquisition of nutrients, which fuel metabolism, growth, and development. Pain signals from these nociceptors are essential for harm avoidance. Dysfunctional TRP channels have been associated with neuropathic pain, inflammation, and reduced ability to detect taste stimuli. Humans have long recognized the relationship between taste and pain. However, the mechanisms and relationship among these taste–pain sensorial experiences are not fully understood. This article provides a narrative review of literature examining the role of TRP channels on taste and pain perception. Genomic variability in the TRPV1 gene has been associated with alterations in various pain conditions. Moreover, polymorphisms of the TRPV1 gene have been associated with alterations in salty taste sensitivity and salt preference. Studies of genetic variations in TRP genes or modulation of TRP pathways may increase our understanding of the shared biological mediators of pain and taste, leading to therapeutic interventions to treat many diseases.

scholarly journals Analgesic Effects of Lipid Raft Disruption by Sphingomyelinase and Myriocin via Transient Receptor Potential Vanilloid 1 and Transient Receptor Potential Ankyrin 1 Ion Channel Modulation

2021 ◽  
Vol 11 ◽  
Author(s):  
Ádám Horváth ◽  
Maja Payrits ◽  
Anita Steib ◽  
Boglárka Kántás ◽  
Tünde Biró-Süt ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lipid Raft ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Membrane Microdomains ◽  
Neuronal Cultures ◽  
Transient Receptor Potential Vanilloid ◽  
Peripheral Sensitization ◽  
Transient Receptor

Transient Receptor Potential (TRP) Vanilloid 1 and Ankyrin 1 (TRPV1, TRPA1) cation channels are expressed in nociceptive primary sensory neurons, and integratively regulate nociceptor and inflammatory functions. Lipid rafts are liquid-ordered plasma membrane microdomains rich in cholesterol, sphingomyelin and gangliosides. We earlier showed that lipid raft disruption inhibits TRPV1 and TRPA1 functions in primary sensory neuronal cultures. Here we investigated the effects of sphingomyelinase (SMase) cleaving membrane sphingomyelin and myriocin (Myr) prohibiting sphingolipid synthesis in mouse pain models of different mechanisms. SMase (50 mU) or Myr (1 mM) pretreatment significantly decreased TRPV1 activation (capsaicin)-induced nocifensive eye-wiping movements by 37 and 41%, respectively. Intraplantar pretreatment by both compounds significantly diminished TRPV1 stimulation (resiniferatoxin)-evoked thermal allodynia developing mainly by peripheral sensitization. SMase (50 mU) also decreased mechanical hyperalgesia related to both peripheral and central sensitizations. SMase (50 mU) significantly reduced TRPA1 activation (formalin)-induced acute nocifensive behaviors by 64% in the second, neurogenic inflammatory phase. Myr, but not SMase altered the plasma membrane polarity related to the cholesterol composition as shown by fluorescence spectroscopy. These are the first in vivo results showing that sphingolipids play a key role in lipid raft integrity around nociceptive TRP channels, their activation and pain sensation. It is concluded that local SMase administration might open novel perspective for analgesic therapy.

scholarly journals Spices to Control COVID-19 Symptoms: Yes, but Not Only…

2020 ◽  
pp. 1-7
Author(s):  
Jean Bousquet ◽  
Wienczyslawa Czarlewski ◽  
Torsten Zuberbier ◽  
Joaquim Mullol ◽  
Hubert Blain ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Oxygen Species ◽  
Large Country ◽  
Death Rates ◽  
Fermented Vegetables ◽  
Transient Receptor ◽  
Transcription Factor Nuclear Factor

There are large country variations in COVID-19 death rates that may be partly explained by diet. Many countries with low COVID-19 death rates have a common feature of eating large quantities of fermented vegetables such as cabbage and, in some continents, various spices. Fermented vegetables and spices are agonists of the antioxidant transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and spices are transient receptor potential ankyrin 1 and vanillin 1 (TRPA1/V1) agonists. These mechanisms may explain many COVID-19 symptoms and severity. It appears that there is a synergy between Nrf2 and TRPA1/V1 foods that may explain the role of diet in COVID-19. One of the mechanisms of COVID-19 appears to be an oxygen species (ROS)-mediated process in synergy with TRP channels, modulated by Nrf2 pathways. Spicy foods are likely to desensitize TRP channels and act in synergy with exogenous antioxidants that activate the Nrf2 pathway.

scholarly journals Phospho-Mimetic Mutation at Ser602 Inactivates Human TRPA1 Channel

2020 ◽  
Vol 21 (21) ◽  
pp. 7995
Author(s):  
Kristyna Barvikova ◽  
Ivan Barvik ◽  
Viktor Sinica ◽  
Lucie Zimova ◽  
Viktorie Vlachova
Keyword(s):  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Conformational Space ◽  
Signaling Cascades ◽  
Post Translational Modifications ◽  
Allosteric Coupling ◽  
Structural Impact ◽  
Transient Receptor

The Transient Receptor Potential Ankyrin 1 (TRPA1) channel is an integrative molecular sensor for detecting environmental irritant compounds, endogenous proalgesic and inflammatory agents, pressure, and temperature. Different post-translational modifications participate in the discrimination of the essential functions of TRPA1 in its physiological environment, but the underlying structural bases are poorly understood. Here, we explored the role of the cytosolic N-terminal residue Ser602 located near a functionally important allosteric coupling domain as a potential target of phosphorylation. The phosphomimetic mutation S602D completely abrogated channel activation, whereas the phosphonull mutations S602G and S602N produced a fully functional channel. Using mutagenesis, electrophysiology, and molecular simulations, we investigated the possible structural impact of a modification (mutation or phosphorylation) of Ser602 and found that this residue represents an important regulatory site through which the intracellular signaling cascades may act to reversibly restrict or “dampen” the conformational space of the TRPA1 channel and promote its transitions to the closed state.

scholarly journals TRP Channels as Drug Targets to Relieve Itch

2018 ◽  
Vol 11 (4) ◽  
pp. 100 ◽  
Author(s):  
Zili Xie ◽  
Hongzhen Hu
Keyword(s):  
Drug Targets ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Current Knowledge ◽  
Receptor Potential ◽  
Protective Role ◽  
Chronic Itch ◽  
Transient Receptor

Although acute itch has a protective role by removing irritants to avoid further damage, chronic itch is debilitating, significantly impacting quality of life. Over the past two decades, a considerable amount of stimulating research has been carried out to delineate mechanisms of itch at the molecular, cellular, and circuit levels. There is growing evidence that transient receptor potential (TRP) channels play important roles in itch signaling. The purpose of this review is to summarize our current knowledge about the role of TRP channels in the generation of itch under both physiological and pathological conditions, thereby identifying them as potential drug targets for effective anti-itch therapies.

Pivotal role of Transient Receptor Potential Channels in oral physiology

2021 ◽  
Vol 28 ◽  
Author(s):  
Andreas Chalazias ◽  
Grigorios Plemmenos ◽  
Evangelos Evangeliou ◽  
Christina Piperi
Keyword(s):  
Salivary Gland ◽  
Oral Cavity ◽  
Periodontal Ligament ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Dental Pain ◽  
Temporomandibular Joints ◽  
Transient Receptor

Background: Transient Receptor Potential (TRP) Channels constitute a large family of non-selective permeable ion channels involved in the perception of environmental stimuli with a central and continuously expanding role in oral tissue homeostasis. Recent studies indicate the regulatory role of TRPs in pulp physiology, oral mucosa sensation, dental pain nociception and salivary gland secretion. This review provides an update on the diverse functions of TRP channels in the physiology of oral cavity, with emphasis on their cellular location, the underlying molecular mechanisms and clinical significance. Methods: A structured search of bibliographic databases (PubMed and MEDLINE) was performed for peer reviewed studies on TRP channels function on oral cavity physiology the last ten years. A qualitative content analysis was performed in screened papers and a critical discussion of main findings is provided. Results: TRPs expression has been detected in major cell types of the oral cavity, including odontoblasts, periodontal ligament, oral epithelial, salivary gland cells, and chondrocytes of temporomandibular joints, where they mediate signal perception and transduction of mechanical, thermal, and osmotic stimuli. They contribute to pulp physiology through dentin formation, mineralization, and periodontal ligament formation along with alveolar bone remodeling in dental pulp and periodontal ligament cells. TRPs are also involved in oral mucosa sensation, dental pain nociception, saliva secretion, swallowing reflex and temporomandibular joints' development. Conclusion: Various TRP channels regulate oral cavity homeostasis, playing an important role in the transduction of external stimuli to intracellular signals in a cell type-specific manner and presenting promising drug targets for the development of pharmacological strategies to manage oral diseases.

scholarly journals Transient Receptor Potential (TRP) Channels in Haematological Malignancies: An Update

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 765
Author(s):  
Federica Maggi ◽  
Maria Beatrice Morelli ◽  
Massimo Nabissi ◽  
Oliviero Marinelli ◽  
Laura Zeppa ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Haematological Malignancy ◽  
Receptor Potential ◽  
Progression Free Survival ◽  
Free Survival ◽  
Channel Expression ◽  
Transient Receptor

Transient receptor potential (TRP) channels are improving their importance in different cancers, becoming suitable as promising candidates for precision medicine. Their important contribution in calcium trafficking inside and outside cells is coming to light from many papers published so far. Encouraging results on the correlation between TRP and overall survival (OS) and progression-free survival (PFS) in cancer patients are available, and there are as many promising data from in vitro studies. For what concerns haematological malignancy, the role of TRPs is still not elucidated, and data regarding TRP channel expression have demonstrated great variability throughout blood cancer so far. Thus, the aim of this review is to highlight the most recent findings on TRP channels in leukaemia and lymphoma, demonstrating their important contribution in the perspective of personalised therapies.

scholarly journals Role of TRP Channels in the Regulation of the Endosomal Pathway

Physiology ◽  
2011 ◽  
Vol 26 (1) ◽  
pp. 14-22 ◽  
Author(s):  
Ken Abe ◽  
Rosa Puertollano
Keyword(s):  
Membrane Trafficking ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Ion Homeostasis ◽  
Receptor Potential ◽  
Trp Channel ◽  
Endosomal Pathway ◽  
Transient Receptor

Some members of the transient receptor potential (TRP) channel superfamily have proved to be essential in maintaining adequate ion homeostasis, signaling, and membrane trafficking in the endosomal pathway. The unique properties of the TRP channels confer cells the ability to integrate cytosolic and intraluminal stimuli and allow maintained and regulated release of Ca2+ from endosomes and lysosomes.

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