Electrophysiological Investigation of Hydrostatic Pressure Mechanotransduction by Urothelial Cell Lines

Trp Channels ◽

Primary Cultures ◽

Receptor Potential ◽

Ruthenium Red ◽

Mechanical Stimuli ◽

Urothelial Cells ◽

Membrane Stretch

The urothelium is the epithelial lining of the ureters, urinary bladder, and urethra. Recent discoveries have suggested that in addition to providing a barrier function to urine, the urothelium actively participates in sensory functions related to thermal, chemical, and mechanical stimuli, and releases chemical signals in response[1]. In addition to a sensitivity to cell membrane stretch caused by wall tension upon bladder filling, in vitro studies by our group have shown that urothelial cells may be sensitive to hydrostatic pressure directly without requiring membrane stretching [2]. Specifically, primary cultures of rat bladder urothelial cells exposed to 10 cmH2O pressure on rigid substrates released significantly greater amounts of ATP compared to the baseline control without exposure to pressure. Moreover, this ATP response by rat urothelial cells to pressure was inhibited by pre-treatment of cells with ruthenium red, a non-specific antagonist of transient receptor potential (TRP) channels, suggesting a potential involvement of these channels in pressure mechanotransduction. Further understanding of the mechanisms, however, is needed to improve treatment of bladder dysfunction such as overactive bladder.

An Optical Approach for Studying the Cellular Mechanotransduction of Hydrostatic Pressure by Bladder Urothelial Cells

ASME 2011 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2011-53872 ◽

2011 ◽

Author(s):

Shawn Olsen ◽

Jiro Nagatomi

Keyword(s):

Ion Channels ◽

Hydrostatic Pressure ◽

Cell Volume ◽

Trp Channels ◽

Receptor Potential ◽

Fluorescent Imaging ◽

Urothelial Cells ◽

Bladder Urothelium

Recent studies have suggested that the bladder urothelium is sensitive to both stretch and hydrostatic pressure during bladder filling, and is considered to play a mechanosensory role in sensing bladder fullness [1, 2]. In a previous study [3], our group demonstrated that compared to the control, rat bladder urothelial cells (UCs) exposed to hydrostatic pressure (10–15 cmH2O for 5 minutes) in vitro released significantly higher levels of ATP and that this response was attenuated by pharmacologically blocking transient receptor potential (TRP) channels, as well as epithelial sodium channels (ENACs). While blocking these ion channels inhibited the ATP response by UCs to hydrostatic pressure, it remains unclear whether these ion channels are being activated directly by hydrostatic pressure or by membrane deformation. Our current hypothesis is that a change in cell volume may occur due to the application of hydrostatic pressure and subsequent changes in cellular osmolality, which, in turn, activate the membrane-bound mechanosensitive channels. Using real-time fluorescent imaging and a custom experimental setup, the present study sought to quantify the UC cell volume changes during exposure to hydrostatic pressure and to better understand the mechanisms by which UCs sense hydrostatic pressure.

Transient Receptor Potential Cation Channels in Cancer Therapy

Medical Sciences ◽

10.3390/medsci7120108 ◽

2019 ◽

Vol 7 (12) ◽

pp. 108 ◽

Cited By ~ 5

Author(s):

Giorgio Santoni ◽

Federica Maggi ◽

Maria Beatrice Morelli ◽

Matteo Santoni ◽

Oliviero Marinelli

Keyword(s):

Cell Proliferation ◽

Cell Death ◽

Cancer Cells ◽

Trp Channels ◽

Receptor Potential ◽

Chemotherapeutic Agents ◽

Migration And Invasion ◽

In mammals, the transient receptor potential (TRP) channels family consists of six different families, namely TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), and TRPA (ankyrin), that are strictly connected with cancer cell proliferation, differentiation, cell death, angiogenesis, migration, and invasion. Changes in TRP channels’ expression and function have been found to regulate cell proliferation and resistance or sensitivity of cancer cells to apoptotic-induced cell death, resulting in cancer-promoting effects or resistance to chemotherapy treatments. This review summarizes the data reported so far on the effect of targeting TRP channels in different types of cancer by using multiple TRP-specific agonists, antagonists alone, or in combination with classic chemotherapeutic agents, microRNA specifically targeting the TRP channels, and so forth, and the in vitro and in vivo feasibility evaluated in experimental models and in cancer patients. Considerable efforts have been made to fight cancer cells, and therapies targeting TRP channels seem to be the most promising strategy. However, more in-depth investigations are required to completely understand the role of TRP channels in cancer in order to design new, more specific, and valuable pharmacological tools.

Camphor, Applied Epidermally to the Back, Causes Snout- and Chest-Grooming in Rats: A Response Mediated by Cutaneous TRP Channels

Pharmaceuticals ◽

10.3390/ph12010024 ◽

2019 ◽

Vol 12 (1) ◽

pp. 24

Author(s):

Débora Ishikawa ◽

Robson Vizin ◽

Cristiane Souza ◽

Daniel Carrettiero ◽

Andrej Romanovsky ◽

...

Keyword(s):

Wistar Rats ◽

Trp Channels ◽

Receptor Potential ◽

Ruthenium Red ◽

The Self ◽

Grooming Behavior ◽

Behavioral Defense ◽

Male Wistar Rats ◽

Thermoregulatory grooming, a behavioral defense against heat, is known to be driven by skin-temperature signals. Because at least some thermal cutaneous signals that drive heat defenses are likely to be generated by transient receptor potential (TRP) channels, we hypothesized that warmth-sensitive TRPs drive thermoregulatory grooming. Adult male Wistar rats were used. We showed that camphor, a nonselective agonist of several TRP channels, including vanilloid (V) 3, when applied epidermally to the back (500 mg/kg), caused a pronounced self-grooming response, including paw-licking and snout- and chest-“washing”. By the percentage of time spent grooming, the response was similar to the thermoregulatory grooming observed during exposure to ambient warmth (32 °C). Ruthenium red (a non-selective antagonist of TRP channels, including TRPV3), when administered intravenously at a dose of 0.1 mg/kg, attenuated the self-grooming behavior induced by either ambient warmth or epidermal camphor. Furthermore, the intravenous administration of AMG8432 (40 mg/kg), a relatively selective TRPV3 antagonist, also attenuated the self-grooming response to epidermal camphor. We conclude that camphor causes the self-grooming behavior by acting on TRP channels in the skin. We propose that cutaneous warmth signals mediated by TRP channels, possibly including TRPV3, drive thermoregulatory self-grooming in rats.

The putative transient receptor potential channel protein encoded by the orf19.4805 gene is involved in cation sensitivity, antifungal tolerance, and filamentation in Candida albicans

Canadian Journal of Microbiology ◽

10.1139/cjm-2018-0048 ◽

2018 ◽

Vol 64 (10) ◽

pp. 727-731 ◽

Cited By ~ 1

Author(s):

Linghuo Jiang ◽

Yi Yang

Keyword(s):

Candida Albicans ◽

Trp Channels ◽

Ion Homeostasis ◽

Sodium Dodecyl ◽

Receptor Potential ◽

Antifungal Drugs ◽

Yeast Saccharomyces Cerevisiae ◽

Transient receptor potential (TRP) channels, an ancient family of cation channels, are highly conserved in eukaryotes and play various physiological functions, ranging from sensation of ion homeostasis to reception of pain and vision. Calcium-permeable TRP channels have been identified from the plant Arabidopsis thaliana (AtCsc1) and the budding yeast Saccharomyces cerevisiae (ScCsc1). In this study, we characterized the functions of the Csc1 homolog, orf19.4805, in Candida albicans. Orf19.4805 is a protein of 866 amino acids and 11 transmembrane domains, which shares 49% identity (69% similarity) in amino acid sequence with ScRsn1. Here, we demonstrate that deletion of the orf19.4805 gene causes C. albicans cells to be sensitive to SDS (sodium dodecyl sulfate) and antifungal drugs, and tolerance to zinc, manganese, and cadmium ions. Candida albicans cells lacking orf19.4805 show a defect in filamentation in vitro. Therefore, orf19.4805 is involved in the regulation of cation homeostasis and filamentation in C. albicans.

911 Transient receptor potential (TRP) channels regulate cell migration of keratinocyte in vitro

Journal of Investigative Dermatology ◽

10.1016/j.jid.2017.02.938 ◽

2017 ◽

Vol 137 (5) ◽

pp. S157

Author(s):

S. Hiroyasu ◽

J.C.R. Jones

Keyword(s):

Cell Migration ◽

Trp Channels ◽

Receptor Potential ◽

TRPV4 Is Required for Hypoxic Pulmonary Vasoconstriction

Anesthesiology ◽

10.1097/aln.0000000000000647 ◽

2015 ◽

Vol 122 (6) ◽

pp. 1338-1348 ◽

Cited By ~ 39

Author(s):

Neil M. Goldenberg ◽

Liming Wang ◽

Hannes Ranke ◽

Wolfgang Liedtke ◽

Arata Tabuchi ◽

...

Keyword(s):

Pulmonary Artery ◽

Intravital Microscopy ◽

Trp Channels ◽

Hypoxic Pulmonary Vasoconstriction ◽

Critical Role ◽

Receptor Potential ◽

Epoxyeicosatrienoic Acid ◽

Pulmonary Vasoconstriction

Abstract Background: Hypoxic pulmonary vasoconstriction (HPV) is critically important in regionally heterogeneous lung diseases by directing blood toward better-oxygenated lung units, yet the molecular mechanism of HPV remains unknown. Transient receptor potential (TRP) channels are a large cation channel family that has been implicated in HPV, specifically in the pulmonary artery smooth muscle cell (PASMC) Ca2+ and contractile response to hypoxia. In this study, the authors probed the role of the TRP family member, TRPV4, in HPV. Methods: HPV was assessed by using isolated perfused mouse lungs or by intravital microscopy to directly visualize pulmonary arterioles in mice. In vitro experiments were performed in primary human PASMC. Results: The hypoxia-induced pulmonary artery pressure increase seen in wild-type mice (5.6 ± 0.6 mmHg; mean ± SEM) was attenuated both by inhibition of TRPV4 (2.8 ± 0.5 mmHg), or in lungs from TRPV4-deficient mice (Trpv4−/−) (3.4 ± 0.5 mmHg; n = 7 each). Functionally, Trpv4−/− mice displayed an exaggerated hypoxemia after regional airway occlusion (pao2 71% of baseline ± 2 vs. 85 ± 2%; n = 5). Direct visualization of pulmonary arterioles by intravital microscopy revealed a 66% reduction in HPV in Trpv4−/− mice. In human PASMC, inhibition of TRPV4 blocked the hypoxia-induced Ca2+ influx and myosin light chain phosphorylation. TRPV4 may form a heteromeric channel with TRPC6 as the two channels coimmunoprecipitate from PASMC and as there is no additive effect of TRPC and TRPV4 inhibition on Ca2+ influx in response to the agonist, 11,12-epoxyeicosatrienoic acid. Conclusion: TRPV4 plays a critical role in HPV, potentially via cooperation with TRPC6.

Transient Receptor Potential Channel Expression Signatures in Tumor-Derived Endothelial Cells: Functional Roles in Prostate Cancer Angiogenesis

Cancers ◽

10.3390/cancers11070956 ◽

2019 ◽

Vol 11 (7) ◽

pp. 956 ◽

Cited By ~ 8

Author(s):

Michela Bernardini ◽

Alessia Brossa ◽

Giorgia Chinigo ◽

Guillaume P. Grolez ◽

Giulia Trimaglio ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Progression ◽

Trp Channels ◽

Receptor Potential ◽

Angiogenic Factor ◽

Renal Tumors ◽

Background: Transient receptor potential (TRP) channels control multiple processes involved in cancer progression by modulating cell proliferation, survival, invasion and intravasation, as well as, endothelial cell (EC) biology and tumor angiogenesis. Nonetheless, a complete TRP expression signature in tumor vessels, including in prostate cancer (PCa), is still lacking. Methods: In the present study, we profiled by qPCR the expression of all TRP channels in human prostate tumor-derived ECs (TECs) in comparison with TECs from breast and renal tumors. We further functionally characterized the role of the ‘prostate-associated’ channels in proliferation, sprout formation and elongation, directed motility guiding, as well as in vitro and in vivo morphogenesis and angiogenesis. Results: We identified three ‘prostate-associated’ genes whose expression is upregulated in prostate TECs: TRPV2 as a positive modulator of TEC proliferation, TRPC3 as an endothelial PCa cell attraction factor and TRPA1 as a critical TEC angiogenic factor in vitro and in vivo. Conclusions: We provide here the full TRP signature of PCa vascularization among which three play a profound effect on EC biology. These results contribute to explain the aggressive phenotype previously observed in PTEC and provide new putative therapeutic targets.

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

Biomolecules ◽

10.3390/biom11050765 ◽

2021 ◽

Vol 11 (5) ◽

pp. 765

Author(s):

Federica Maggi ◽

Maria Beatrice Morelli ◽

Massimo Nabissi ◽

Oliviero Marinelli ◽

Laura Zeppa ◽

...

Keyword(s):

Trp Channels ◽

Haematological Malignancy ◽

Receptor Potential ◽

Progression Free Survival ◽

Free Survival ◽

Channel Expression ◽

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.

Expression profiles of TRPV1, TRPV4, TLR4 and ERK1/2 in the dorsal root ganglionic neurons of a cancer-induced neuropathy rat model

PeerJ ◽

10.7717/peerj.4622 ◽

2018 ◽

Vol 6 ◽

pp. e4622 ◽

Cited By ~ 8

Author(s):

Ahmad Maqboul ◽

Bakheet Elsadek

Keyword(s):

Calcium Ions ◽

Dorsal Root ◽

Trp Channels ◽

Expression Profiles ◽

Receptor Potential ◽

Ruthenium Red ◽

Mechanical Hyperalgesia ◽

Transient Receptor Potential Vanilloid ◽

Background The spread of tumors through neural routes is common in several types of cancer in which patients suffer from a moderate-to-severe neuropathy, neural damage and a distorted quality of life. Here we aim to examine the expression profiles of transient receptor potential vanilloid 1 (TRPV1) and of transient receptor potential vanilloid 4 (TRPV4), toll-like receptor 4 (TLR4) and extracellular signal-regulated kinase (ERK1/2), and to assess the possible therapeutic strategies through blockade of transient receptor potential (TRP) channels. Methods Cancer was induced within the sciatic nerves of male Copenhagen rats, and tissues from dorsal root ganglia (DRG) were collected and used for measurements of immunofluorescence and Western blotting. The TRPV1 antagonist capsazepine, the selective TRPV4 antagonist HC-067047 and the calcium ions inhibitor ruthenium red were used to treat thermal and/or mechanical hyperalgesia. Results Transient receptor potential vanilloid 1 showed a lower expression in DRGs on days 7 and 14. The expression of TRPV4, TLR4 and ERK1/2 showed an increase on day 3 then a decrease on days 7 and 14. TRPV1 and TLR4 as well as TRPV4 and ERK1/2 co-existed on the same neuronal cells. The neuropathic pain was reversed in dose-dependent manners by using the TRP antagonists and the calcium ions inhibitor. Conclusion The decreased expression of TRPV1 and TRPV4 is associated with high activation. The increased expression of TLR4 and ERK1/2 reveals earlier immune response and tumor progression, respectively, and their ultimate decrease is an indicator of nerve damage. We studied the possible role of TRPV1 and TRPV4 in transducing cancer-induced hyperalgesia. The possible treatment strategies of cancer-induced thermal and/or mechanical hyperalgesia using capsazepine, HC-067047 and ruthenium red are examined.

Injury-induced cold sensitization in Drosophila larvae involves behavioral shifts that require the TRP channels Pkd2 and Brv1

10.1101/342717 ◽

2018 ◽

Author(s):

Heather N. Turner ◽

Atit A. Patel ◽

Daniel N. Cox ◽

Michael J. Galko

Keyword(s):

Tissue Damage ◽

Trp Channels ◽

Molecular Genetic ◽

Receptor Potential ◽

Cellular Level ◽

Mechanical Stimuli ◽

Class Iii ◽

Sensory Stimuli ◽

Nociceptive Sensitization

AbstractNociceptive sensitization involves an increase in responsiveness of pain sensing neurons to sensory stimuli, typically through the lowering of their nociceptive threshold. Nociceptive sensitization is common following tissue damage, inflammation, and disease and serves to protect the affected area while it heals. Organisms can become sensitized to a range of noxious and innocuous stimuli, including thermal stimuli. The basic mechanisms underlying sensitization to warm or painfully hot stimuli have begun to be elucidated, however, sensitization to cold is not well understood. Here, we develop a Drosophila assay to study cold sensitization after UV-induced epidermal damage in larvae. Larvae respond to acute cold stimuli with a set of unique behaviors that include a contraction of the head and tail (CT) or a raising of the head and tail into a U-Shape (US). Under baseline, non-injured conditions larvae primarily produce a CT response to an acute cold (10 °C) stimulus, however, we show that cold-evoked responses shift following tissue damage: CT responses decrease, US responses increase and some larvae exhibit a lateral body roll (BR) that is typically only observed in response to high temperature and noxious mechanical stimuli. At the cellular level, class III neurons are required for the decrease in CT, chordotonal neurons are required for the increase in US, and chordotonal and class IV neurons are required for the appearance of BR responses after UV. At the molecular level, we found that the transient receptor potential (TRP) channels Polycystic kidney disease gene 2 (Pkd2) and brivido-1 (brv1) are required for these behavioral shifts. Our Drosophila model will enable a sophisticated molecular genetic dissection of genes and circuits involved in cold nociceptive sensitization.