scholarly journals Scraping through the ice: uncovering the role of TRPM8 in cold transduction

2011 ◽  
Vol 300 (6) ◽  
pp. R1278-R1287 ◽  
Author(s):  
Daniel D. McCoy ◽  
Wendy M. Knowlton ◽  
David D. McKemy
Keyword(s):  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Temperature Sensitive ◽  
Cellular Mechanisms ◽  
Ongoing Research ◽  
Peripheral Tissues

The proper detection of environmental temperatures is essential for the optimal growth and survival of organisms of all shapes and phyla, yet only recently have the molecular mechanisms for temperature sensing been elucidated. The discovery of temperature-sensitive ion channels of the transient receptor potential (TRP) superfamily has been pivotal in explaining how temperatures are sensed in vivo, and here we will focus on the lone member of this cohort, TRPM8, which has been unequivocally shown to be cold sensitive. TRPM8 is expressed in somatosensory neurons that innervate peripheral tissues such as the skin and oral cavity, and recent genetic evidence has shown it to be the principal transducer of cool and cold stimuli. It is remarkable that this one channel, unlike other thermosensitive TRP channels, is associated with both innocuous and noxious temperature transduction, as well as cold hypersensitivity during injury and, paradoxically, cold-mediated analgesia. With ongoing research, the field is getting closer to answering a number of fundamental questions regarding this channel, including the cellular mechanisms of TRPM8 modulation, the molecular context of TRPM8 expression, as well as the full extent of the role of TRPM8 in cold signaling in vivo. These findings will further our understanding of basic thermotransduction and sensory coding, and may have important implications for treatments for acute and chronic pain.

scholarly journals Differential role of TRP channels in prostate cancer

2007 ◽  
Vol 35 (1) ◽  
pp. 133-135 ◽  
Author(s):  
N. Prevarskaya ◽  
M. Flourakis ◽  
G. Bidaux ◽  
S. Thebault ◽  
R. Skryma
Keyword(s):  
Prostate Cancer ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Clinical Problem ◽  
Tissue Growth ◽  
Transient Receptor Potential Channels ◽  
Potential Channels ◽  
Differentiation And Proliferation

A major clinical problem with PC (prostate cancer) is the cell's ability to survive and proliferate upon androgen withdrawal. Indeed, deregulated cell differentiation and proliferation, together with the suppression of apoptosis, provides the condition for abnormal tissue growth. Here, we examine the differential role of TRP (transient receptor potential) channels in the control of Ca2+ homoeostasis and growth of PC cells.

scholarly journals TRPC1 participates in the HSV-1 infection process by facilitating viral entry

2020 ◽  
Vol 6 (12) ◽  
pp. eaaz3367 ◽  
Author(s):  
DongXu He ◽  
AiQin Mao ◽  
YouRan Li ◽  
SiuCheung Tam ◽  
YongTang Zheng ◽  
...  
Keyword(s):  
Viral Entry ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Critical Role ◽  
Receptor Potential ◽  
Infection Process ◽  
Ocular Abnormality ◽  
Simplex Virus ◽  
Hsv 1

Mammalian transient receptor potential (TRP) channels are major components of Ca2+ signaling pathways and control a diversity of physiological functions. Here, we report a specific role for TRPC1 in the entry of herpes simplex virus type 1 (HSV-1) into cells. HSV-1–induced Ca2+ release and entry were dependent on Orai1, STIM1, and TRPC1. Inhibition of Ca2+ entry or knockdown of these proteins attenuated viral entry and infection. HSV-1 glycoprotein D interacted with the third ectodomain of TRPC1, and this interaction facilitated viral entry. Knockout of TRPC1 attenuated HSV-1–induced ocular abnormality and morbidity in vivo in TRPC1−/− mice. There was a strong correlation between HSV-1 infection and plasma membrane localization of TRPC1 in epithelial cells within oral lesions in buccal biopsies from HSV-1–infected patients. Together, our findings demonstrate a critical role for TRPC1 in HSV-1 infection and suggest the channel as a potential target for anti-HSV therapy.

Thermoregulation: some concepts have changed. Functional architecture of the thermoregulatory system

2007 ◽  
Vol 292 (1) ◽  
pp. R37-R46 ◽  
Author(s):  
Andrej A. Romanovsky
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Open Loop ◽  
Temperature Sensitive ◽  
Functional Architecture ◽  
Set Point ◽  
Sequential Activation ◽  
Thermoregulatory System ◽  
Transient Receptor

While summarizing the current understanding of how body temperature (Tb) is regulated, this review discusses the recent progress in the following areas: central and peripheral thermosensitivity and temperature-activated transient receptor potential (TRP) channels; afferent neuronal pathways from peripheral thermosensors; and efferent thermoeffector pathways. It is proposed that activation of temperature-sensitive TRP channels is a mechanism of peripheral thermosensitivity. Special attention is paid to the functional architecture of the thermoregulatory system. The notion that deep Tb is regulated by a unified system with a single controller is rejected. It is proposed that Tb is regulated by independent thermoeffector loops, each having its own afferent and efferent branches. The activity of each thermoeffector is triggered by a unique combination of shell and core Tbs. Temperature-dependent phase transitions in thermosensory neurons cause sequential activation of all neurons of the corresponding thermoeffector loop and eventually a thermoeffector response. No computation of an integrated Tb or its comparison with an obvious or hidden set point of a unified system is necessary. Coordination between thermoeffectors is achieved through their common controlled variable, Tb. The described model incorporates Kobayashi’s views, but Kobayashi’s proposal to eliminate the term sensor is rejected. A case against the term set point is also made. Because this term is historically associated with a unified control system, it is more misleading than informative. The term balance point is proposed to designate the regulated level of Tb and to attract attention to the multiple feedback, feedforward, and open-loop components that contribute to thermal balance.

scholarly journals Transient Receptor Potential Channels as an Emerging Target for the Treatment of Parkinson’s Disease: An Insight Into Role of Pharmacological Interventions

2020 ◽  
Vol 8 ◽  
Author(s):  
Bhupesh Vaidya ◽  
Shyam Sunder Sharma
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Neurodegenerative Disorder ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Transient Receptor

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the symptoms of motor deficits and cognitive decline. There are a number of therapeutics available for the treatment of PD, but most of them suffer from serious side effects such as bradykinesia, dyskinesia and on-off effect. Therefore, despite the availability of these pharmacological agents, PD patients continue to have an inferior quality of life. This has warranted a need to look for alternate strategies and molecular targets. Recent evidence suggests the Transient Receptor Potential (TRP) channels could be a potential target for the management of motor and non-motor symptoms of PD. Though still in the preclinical stages, agents targeting these channels have shown immense potential in the attenuation of behavioral deficits and signaling pathways. In addition, these channels are known to be involved in the regulation of ionic homeostasis, which is disrupted in PD. Moreover, activation or inhibition of many of the TRP channels by calcium and oxidative stress has also raised the possibility of their paramount involvement in affecting the other molecular mechanisms associated with PD pathology. However, due to the paucity of information available and lack of specificity, none of these agents have gone into clinical trials for PD treatment. Considering their interaction with oxidative stress, apoptosis and excitotoxicity, TRP channels could be considered as a potential future target for the treatment of PD.

scholarly journals Epithelial transient receptor potential ankyrin 1 (TRPA1)-dependent adrenomedullin upregulates blood flow in rat small intestine

2013 ◽  
Vol 304 (4) ◽  
pp. G428-G436 ◽  
Author(s):  
Toru Kono ◽  
Atsushi Kaneko ◽  
Yuji Omiya ◽  
Katsuya Ohbuchi ◽  
Nagisa Ohno ◽  
...  
Keyword(s):  
Blood Flow ◽  
Small Intestine ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Allyl Isothiocyanate ◽  
Antibody Treatment ◽  
Functional Roles ◽  
Transient Receptor

The functional roles of transient receptor potential (TRP) channels in the gastrointestinal tract have garnered considerable attention in recent years. We previously reported that daikenchuto (TU-100), a traditional Japanese herbal medicine, increased intestinal blood flow (IBF) via adrenomedullin (ADM) release from intestinal epithelial (IE) cells (Kono T et al. J Crohns Colitis 4: 161–170, 2010). TU-100 contains multiple TRP activators. In the present study, therefore, we examined the involvement of TRP channels in the ADM-mediated vasodilatatory effect of TU-100. Rats were treated intraduodenally with the TRP vanilloid type 1 (TRPV1) agonist capsaicin (CAP), the TRP ankyrin 1 (TRPA1) agonist allyl-isothiocyanate (AITC), or TU-100, and jejunum IBF was evaluated using laser-Doppler blood flowmetry. All three compounds resulted in vasodilatation, and the vasodilatory effect of TU-100 was abolished by a TRPA1 antagonist but not by a TRPV1 antagonist. Vasodilatation induced by AITC and TU-100 was abrogated by anti-ADM antibody treatment. RT-PCR and flow cytometry revealed that an IEC-6 cell line originated from the small intestine and purified IE cells expressed ADM and TRPA1 but not TRPV1. AITC increased ADM release in IEC cells remarkably, while CAP had no effect. TU-100 and its ingredient 6-shogaol (6SG) increased ADM release dose-dependently, and the effects were abrogated by a TRPA1 antagonist. 6SG showed similar TRPA1-dependent vasodilatation in vivo. These results indicate that TRPA1 in IE cells may play an important role in controlling bowel microcirculation via ADM release. Epithelial TRPA1 appears to be a promising target for the development of novel strategies for the treatment of various gastrointestinal disorders.

scholarly journals Canonical Transient Receptor Potential (TRPC) 1 Acts as a Negative Regulator for Vanilloid TRPV6-mediated Ca2+ Influx

2012 ◽  
Vol 287 (42) ◽  
pp. 35612-35620 ◽  
Author(s):  
Rainer Schindl ◽  
Reinhard Fritsch ◽  
Isaac Jardin ◽  
Irene Frischauf ◽  
Heike Kahr ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Negative Regulator ◽  
Hek293 Cells ◽  
Current Voltage ◽  
Repeat Domain ◽  
Transient Receptor ◽  
Current Voltage Relationship

TRP proteins mostly assemble to homomeric channels but can also heteromerize, preferentially within their subfamilies. The TRPC1 protein is the most versatile member and forms various TRPC channel combinations but also unique channels with the distantly related TRPP2 and TRPV4. We show here a novel cross-family interaction between TRPC1 and TRPV6, a Ca2+ selective member of the vanilloid TRP subfamily. TRPV6 exhibited substantial co-localization and in vivo interaction with TRPC1 in HEK293 cells, however, no interaction was observed with TRPC3, TRPC4, or TRPC5. Ca2+ and Na+ currents of TRPV6-overexpressing HEK293 cells are significantly reduced by co-expression of TRPC1, correlating with a dramatically suppressed plasma membrane targeting of TRPV6. In line with their intracellular retention, remaining currents of TRPC1 and TRPV6 co-expression resemble in current-voltage relationship that of TRPV6. Studying the N-terminal ankyrin like repeat domain, structurally similar in the two proteins, we have found that these cytosolic segments were sufficient to mediate a direct heteromeric interaction. Moreover, the inhibitory role of TRPC1 on TRPV6 influx was also maintained by expression of only its N-terminal ankyrin-like repeat domain. Our experiments provide evidence for a functional interaction of TRPC1 with TRPV6 that negatively regulates Ca2+ influx in HEK293 cells.

scholarly journals The Role of Transient Receptor Potential (TRP) Channels in the Transduction of Dental Pain

2019 ◽  
Vol 20 (3) ◽  
pp. 526 ◽  
Author(s):  
Mohammad Hossain ◽  
Marina Bakri ◽  
Farhana Yahya ◽  
Hiroshi Ando ◽  
Shumpei Unno ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Glutamate Release ◽  
Receptor Potential ◽  
Functional Expression ◽  
Dental Pain ◽  
Post Translational Modifications ◽  
Transient Receptor ◽  
External Stimuli

Dental pain is a common health problem that negatively impacts the activities of daily living. Dentine hypersensitivity and pulpitis-associated pain are among the most common types of dental pain. Patients with these conditions feel pain upon exposure of the affected tooth to various external stimuli. However, the molecular mechanisms underlying dental pain, especially the transduction of external stimuli to electrical signals in the nerve, remain unclear. Numerous ion channels and receptors localized in the dental primary afferent neurons (DPAs) and odontoblasts have been implicated in the transduction of dental pain, and functional expression of various polymodal transient receptor potential (TRP) channels has been detected in DPAs and odontoblasts. External stimuli-induced dentinal tubular fluid movement can activate TRP channels on DPAs and odontoblasts. The odontoblasts can in turn activate the DPAs by paracrine signaling through ATP and glutamate release. In pulpitis, inflammatory mediators may sensitize the DPAs. They could also induce post-translational modifications of TRP channels, increase trafficking of these channels to nerve terminals, and increase the sensitivity of these channels to stimuli. Additionally, in caries-induced pulpitis, bacterial products can directly activate TRP channels on DPAs. In this review, we provide an overview of the TRP channels expressed in the various tooth structures, and we discuss their involvement in the development of dental pain.

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.

Calciotropic and Magnesiotropic TRP Channels

Physiology ◽  
2008 ◽  
Vol 23 (1) ◽  
pp. 32-40 ◽  
Author(s):  
Joost G. J. Hoenderop ◽  
René J. M. Bindels
Keyword(s):  
Divalent Cation ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Significant Progress ◽  
Functional Aspects ◽  
Health And Disease ◽  
Transient Receptor

Significant progress has been made into our understanding of the molecular mechanisms responsible for Ca2+ and Mg2+ homeostasis. Members of the transient receptor potential channel (TRP) superfamily proved essential to the maintenance of divalent cation levels by regulating their absorption from renal and intestinal lumina. This review highlights the molecular and functional aspects of these new calciotropic and magnesiotropic TRPs in health and disease.

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