Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
4.7
4.6
Journals
Pharmaceuticals
Special Issues
Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts...
share announcement

Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (1 June 2016) | Viewed by 144050

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Arpad Szallasi

grade E-Mail Website
Guest Editor
Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary
Interests: the capsaicin receptor TRPV1; small molecule TRP inhibitors; TRP channels and cancer; neurogenic inflammation and cancer; cancer pain
Special Issues, Collections and Topics in MDPI journals
Dr. Susan M. Huang

E-Mail
Co-Guest Editor
AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA

Special Issue Information

Dear Colleagues,

Next year will mark the 20th anniversary of the 1997 molecular cloning of the vanilloid (capsaicin) receptor TRPV1. This seminal finding has opened up a new chapter in drug discovery efforts and initiated an unprecedented investment by pharma into drug development. Indeed, the first TRPV1 antagonists were ushered into clinical trials with record speed where most flamed out to great disappointment due to a combination of unforeseen side-effects and lack of clinical efficacy. Meanwhile, other TRP channels have emerged as promising therapeutic targets. At present, TRPA1 (pain, cough), TRPV3 (pain), and TRPM8 (prostate cancer) are being tested in patients, and other TRP channels are probably not far behind. To review twenty years of relentless progress in the TRP channel field, the journal Pharmaceuticals now invites both review articles and originals findings. Invited reviews are listed below. This collection of manuscripts will be published as a Special Issue in the journal first, and hopefully as an eBook later on. Please, email either Susan Huang or Arpad Szallasi if you would like to contribute a paper to this TRP channel issue.

Dr. Arpad Szallasi
Guest Editor

Dr. Susan M. Huang
Co-Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • TRP channels
  • capsaicin
  • resiniferatoxin
  • TRPV1
  • TRPV3
  • TRPA1
  • TRPM2
  • TRPM7
  • TRPM8
  • pain
  • permanent analgesia
  • diabetes
  • obesity
  • cancer
  • respiratory disorders

Related Special Issues

Published Papers (16 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Review

161 KiB  
Editorial
Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts
by Susan Huang and Arpad Szallasi
Pharmaceuticals 2017, 10(3), 64; https://doi.org/10.3390/ph10030064 - 06 Jul 2017
Cited by 13 | Viewed by 4760
Abstract
2017 marks the 20th anniversary of the molecular cloning by David Julius and colleagues (1997) of the long sought-after capsaicin receptor, now known as TRPV1 (Transient Receptor Potential Vanilloid 1) [1]. This seminal discovery has opened up a “hot” new field of basic [...] Read more.
2017 marks the 20th anniversary of the molecular cloning by David Julius and colleagues (1997) of the long sought-after capsaicin receptor, now known as TRPV1 (Transient Receptor Potential Vanilloid 1) [1]. This seminal discovery has opened up a “hot” new field of basic research and launched drug discovery efforts into the large family (by the latest count 28 mammalian members, 27 in humans) of TRP ion channels [2]. Indeed, it took less than a decade for the first potent, small molecule TRPV1 antagonists to enter phase 1 clinical trials [3]. Yet, despite the large amount of resources that has been invested in TRPV1 research, there are currently no TRPV1-targeted drugs in phase 3 clinical trials. In this special issue of Pharmaceuticals, we aim to capture the progress in the TRP channel field over the past twenty years, with 15 articles covering a variety of TRP channels and potential relevant disease states and applications. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)

Review

Jump to: Editorial

1637 KiB  
Review
Role of TRPM7 in Cancer: Potential as Molecular Biomarker and Therapeutic Target
by Nelson S. Yee
Pharmaceuticals 2017, 10(2), 39; https://doi.org/10.3390/ph10020039 - 05 Apr 2017
Cited by 67 | Viewed by 8444
Abstract
The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed ion channel with intrinsic kinase activity. Molecular and electrophysiological analyses of the structure and activity of TRPM7 have revealed functional coupling of its channel and kinase activity. Studies have indicated the [...] Read more.
The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed ion channel with intrinsic kinase activity. Molecular and electrophysiological analyses of the structure and activity of TRPM7 have revealed functional coupling of its channel and kinase activity. Studies have indicated the important roles of TRPM7 channel-kinase in fundamental cellular processes, physiological responses, and embryonic development. Accumulating evidence has shown that TRPM7 is aberrantly expressed and/or activated in human diseases including cancer. TRPM7 plays a variety of functional roles in cancer cells including survival, cell cycle progression, proliferation, growth, migration, invasion, and epithelial-mesenchymal transition (EMT). Data from a study using mouse xenograft of human cancer show that TRPM7 is required for tumor growth and metastasis. The aberrant expression of TRPM7 and its genetic mutations/polymorphisms have been identified in various types of carcinoma. Chemical modulators of TRPM7 channel produced inhibition of proliferation, growth, migration, invasion, invadosome formation, and markers of EMT in cancer cells. Taken together, these studies suggest the potential value of exploiting TRPM7 channel-kinase as a molecular biomarker and therapeutic target in human malignancies. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
►▼ Show Figures

Figure 1

212 KiB  
Review
Development of TRPM8 Antagonists to Treat Chronic Pain and Migraine
by Andy D. Weyer and Sonya G. Lehto
Pharmaceuticals 2017, 10(2), 37; https://doi.org/10.3390/ph10020037 - 30 Mar 2017
Cited by 69 | Viewed by 6601
Abstract
A review. Development of pharmaceutical antagonists of transient receptor potential melastatin 8 (TRPM8) have been pursued for the treatment of chronic pain and migraine. This review focuses on the current state of this progress. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
507 KiB  
Review
Modulation of TRP Channel Activity by Hydroxylation and Its Therapeutic Potential
by Yagnesh Nagarajan, Grigori Y. Rychkov and Daniel J. Peet
Pharmaceuticals 2017, 10(2), 35; https://doi.org/10.3390/ph10020035 - 27 Mar 2017
Cited by 8 | Viewed by 5227
Abstract
Two transient receptor potential (TRP) channels—TRPA1 and TRPV3—are post-translationally hydroxylated, resulting in oxygen-dependent regulation of channel activity. The enzymes responsible are the HIF prolyl hydroxylases (PHDs) and the asparaginyl hydroxylase factor inhibiting HIF (FIH). The PHDs and FIH are well characterized for their [...] Read more.
Two transient receptor potential (TRP) channels—TRPA1 and TRPV3—are post-translationally hydroxylated, resulting in oxygen-dependent regulation of channel activity. The enzymes responsible are the HIF prolyl hydroxylases (PHDs) and the asparaginyl hydroxylase factor inhibiting HIF (FIH). The PHDs and FIH are well characterized for their hydroxylation of the hypoxic inducible transcription factors (HIFs), mediating their hypoxic regulation. Consequently, these hydroxylases are currently being targeted therapeutically to modulate HIF activity in anemia, inflammation, and ischemic disease. Modulating the HIFs by targeting these hydroxylases may result in both desirable and undesirable effects on TRP channel activity, depending on the physiological context. For the best outcomes, these hydroxylases could be therapeutically targeted in pathologies where activation of both the HIFs and the relevant TRP channels are predicted to independently achieve positive outcomes, such as wound healing and obesity. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
►▼ Show Figures

Figure 1

513 KiB  
Review
TRP Channels in Skin Biology and Pathophysiology
by Michael J. Caterina and Zixuan Pang
Pharmaceuticals 2016, 9(4), 77; https://doi.org/10.3390/ph9040077 - 14 Dec 2016
Cited by 123 | Viewed by 12787
Abstract
Ion channels of the Transient Receptor Potential (TRP) family mediate the influx of monovalent and/or divalent cations into cells in response to a host of chemical or physical stimuli. In the skin, TRP channels are expressed in many cell types, including keratinocytes, sensory [...] Read more.
Ion channels of the Transient Receptor Potential (TRP) family mediate the influx of monovalent and/or divalent cations into cells in response to a host of chemical or physical stimuli. In the skin, TRP channels are expressed in many cell types, including keratinocytes, sensory neurons, melanocytes, and immune/inflammatory cells. Within these diverse cell types, TRP channels participate in physiological processes ranging from sensation to skin homeostasis. In addition, there is a growing body of evidence implicating abnormal TRP channel function, as a product of excessive or deficient channel activity, in pathological skin conditions such as chronic pain and itch, dermatitis, vitiligo, alopecia, wound healing, skin carcinogenesis, and skin barrier compromise. These diverse functions, coupled with the fact that many TRP channels possess pharmacologically accessible sites, make this family of proteins appealing therapeutic targets for skin disorders. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
►▼ Show Figures

Figure 1

1141 KiB  
Review
Nociceptive TRP Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies
by Aaron D. Mickle, Andrew J. Shepherd and Durga P. Mohapatra
Pharmaceuticals 2016, 9(4), 72; https://doi.org/10.3390/ph9040072 - 14 Nov 2016
Cited by 96 | Viewed by 13363
Abstract
Specialized receptors belonging to the transient receptor potential (TRP) family of ligand-gated ion channels constitute the critical detectors and transducers of pain-causing stimuli. Nociceptive TRP channels are predominantly expressed by distinct subsets of sensory neurons of the peripheral nervous system. Several of these [...] Read more.
Specialized receptors belonging to the transient receptor potential (TRP) family of ligand-gated ion channels constitute the critical detectors and transducers of pain-causing stimuli. Nociceptive TRP channels are predominantly expressed by distinct subsets of sensory neurons of the peripheral nervous system. Several of these TRP channels are also expressed in neurons of the central nervous system, and in non-neuronal cells that communicate with sensory nerves. Nociceptive TRPs are activated by specific physico-chemical stimuli to provide the excitatory trigger in neurons. In addition, decades of research has identified a large number of immune and neuromodulators as mediators of nociceptive TRP channel activation during injury, inflammatory and other pathological conditions. These findings have led to aggressive targeting of TRP channels for the development of new-generation analgesics. This review summarizes the complex activation and/or modulation of nociceptive TRP channels under pathophysiological conditions, and how these changes underlie acute and chronic pain conditions. Furthermore, development of small-molecule antagonists for several TRP channels as analgesics, and the positive and negative outcomes of these drugs in clinical trials are discussed. Understanding the diverse functional and modulatory properties of nociceptive TRP channels is critical to function-based drug targeting for the development of evidence-based and efficacious new generation analgesics. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
►▼ Show Figures

Figure 1

732 KiB  
Review
Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise?
by Indranil Mukhopadhyay, Abhay Kulkarni and Neelima Khairatkar-Joshi
Pharmaceuticals 2016, 9(4), 70; https://doi.org/10.3390/ph9040070 - 05 Nov 2016
Cited by 34 | Viewed by 7209
Abstract
Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli. [...] Read more.
Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli. Functional presence of TRPA1 on non-neuronal cells got recognized recently. TRPA1 plays a well-recognized role of “chemosensor”, detecting presence of exogenous irritants and endogenous pro-inflammatory mediators that are implicated in airway inflammation and sensory symptoms like chronic cough, asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis and cystic fibrosis. TRPA1 can remain activated chronically due to elevated levels and continued presence of such endogenous ligands and pro-inflammatory mediators. Several selective TRPA1 antagonists have been tested in animal models of respiratory disease and their performance is very promising. Although there is no TRPA1 antagonist in advanced clinical trials or approved on market yet to treat respiratory diseases, however, limited but promising evidences available so far indicate likelihood that targeting TRPA1 may present a new therapy in treatment of respiratory diseases in near future. This review will focus on in vitro, animal and human evidences that strengthen the proposed role of TRPA1 in modulation of specific airway sensory responses and also on preclinical and clinical progress of selected TRPA1 antagonists. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
►▼ Show Figures

Figure 1

756 KiB  
Review
Use of Capsaicin to Treat Pain: Mechanistic and Therapeutic Considerations
by Man-Kyo Chung and James N. Campbell
Pharmaceuticals 2016, 9(4), 66; https://doi.org/10.3390/ph9040066 - 01 Nov 2016
Cited by 73 | Viewed by 20222
Abstract
Capsaicin is the pungent ingredient of chili peppers and is approved as a topical treatment of neuropathic pain. The analgesia lasts for several months after a single treatment. Capsaicin selectively activates TRPV1, a Ca2+-permeable cationic ion channel that is enriched in [...] Read more.
Capsaicin is the pungent ingredient of chili peppers and is approved as a topical treatment of neuropathic pain. The analgesia lasts for several months after a single treatment. Capsaicin selectively activates TRPV1, a Ca2+-permeable cationic ion channel that is enriched in the terminals of certain nociceptors. Activation is followed by a prolonged decreased response to noxious stimuli. Interest also exists in the use of injectable capsaicin as a treatment for focal pain conditions, such as arthritis and other musculoskeletal conditions. Recently injection of capsaicin showed therapeutic efficacy in patients with Morton’s neuroma, a painful foot condition associated with compression of one of the digital nerves. The relief of pain was associated with no change in tactile sensibility. Though injection evokes short term pain, the brief systemic exposure and potential to establish long term analgesia without other sensory changes creates an attractive clinical profile. Short-term and long-term effects arise from both functional and structural changes in nociceptive terminals. In this review, we discuss how local administration of capsaicin may induce ablation of nociceptive terminals and the clinical implications. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
►▼ Show Figures

Figure 1

4037 KiB  
Review
TRPV3 in Drug Development
by Lisa M. Broad, Adrian J. Mogg, Elizabeth Eberle, Marcia Tolley, Dominic L. Li and Kelly L. Knopp
Pharmaceuticals 2016, 9(3), 55; https://doi.org/10.3390/ph9030055 - 09 Sep 2016
Cited by 51 | Viewed by 10073
Abstract
Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP (Transient Receptor Potential) super-family. It is a relatively underexplored member of the thermo-TRP sub-family (Figure 1), however, genetic mutations and use of gene knock-outs and selective pharmacological tools are [...] Read more.
Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP (Transient Receptor Potential) super-family. It is a relatively underexplored member of the thermo-TRP sub-family (Figure 1), however, genetic mutations and use of gene knock-outs and selective pharmacological tools are helping to provide insights into its role and therapeutic potential. TRPV3 is highly expressed in skin, where it is implicated in skin physiology and pathophysiology, thermo-sensing and nociception. Gain of function TRPV3 mutations in rodent and man have enabled the role of TRPV3 in skin health and disease to be particularly well defined. Pre-clinical studies provide some rationale to support development of TRPV3 antagonists for therapeutic application for the treatment of inflammatory skin conditions, itch and pain. However, to date, only one compound directed towards block of the TRPV3 receptor (GRC15300) has progressed into clinical trials. Currently, there are no known clinical trials in progress employing a TRPV3 antagonist. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
►▼ Show Figures

Figure 1

1067 KiB  
Review
Targeting TRPM2 in ROS-Coupled Diseases
by Shinichiro Yamamoto and Shunichi Shimizu
Pharmaceuticals 2016, 9(3), 57; https://doi.org/10.3390/ph9030057 - 07 Sep 2016
Cited by 33 | Viewed by 7961
Abstract
Under pathological conditions such as inflammation and ischemia-reperfusion injury large amounts of reactive oxygen species (ROS) are generated which, in return, contribute to the development and exacerbation of disease. The second member of the transient receptor potential (TRP) melastatin subfamily, TRPM2, is a [...] Read more.
Under pathological conditions such as inflammation and ischemia-reperfusion injury large amounts of reactive oxygen species (ROS) are generated which, in return, contribute to the development and exacerbation of disease. The second member of the transient receptor potential (TRP) melastatin subfamily, TRPM2, is a Ca2+-permeable non-selective cation channel, activated by ROS in an ADP-ribose mediated fashion. In other words, TRPM2 functions as a transducer that converts oxidative stress into Ca2+ signaling. There is good evidence that TRPM2 plays an important role in ROS-coupled diseases. For example, in monocytes the influx of Ca2+ through TRPM2 activated by ROS contributes to the aggravation of inflammation via chemokine production. In this review, the focus is on TRPM2 as a molecular linker between ROS and Ca2+ signaling in ROS-coupled diseases. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
►▼ Show Figures

Figure 1

1308 KiB  
Review
TRPV1: A Target for Rational Drug Design
by Vincenzo Carnevale and Tibor Rohacs
Pharmaceuticals 2016, 9(3), 52; https://doi.org/10.3390/ph9030052 - 23 Aug 2016
Cited by 81 | Viewed by 11876
Abstract
Transient Receptor Potential Vanilloid 1 (TRPV1) is a non-selective, Ca2+ permeable cation channel activated by noxious heat, and chemical ligands, such as capsaicin and resiniferatoxin (RTX). Many compounds have been developed that either activate or inhibit TRPV1, but none of them are [...] Read more.
Transient Receptor Potential Vanilloid 1 (TRPV1) is a non-selective, Ca2+ permeable cation channel activated by noxious heat, and chemical ligands, such as capsaicin and resiniferatoxin (RTX). Many compounds have been developed that either activate or inhibit TRPV1, but none of them are in routine clinical practice. This review will discuss the rationale for antagonists and agonists of TRPV1 for pain relief and other conditions, and strategies to develop new, better drugs to target this ion channel, using the newly available high-resolution structures. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
►▼ Show Figures

Figure 1

254 KiB  
Review
TRP Channels as Therapeutic Targets in Diabetes and Obesity
by Andrea Zsombok and Andrei V. Derbenev
Pharmaceuticals 2016, 9(3), 50; https://doi.org/10.3390/ph9030050 - 17 Aug 2016
Cited by 33 | Viewed by 6483
Abstract
During the last three to four decades the prevalence of obesity and diabetes mellitus has greatly increased worldwide, including in the United States. Both the short- and long-term forecasts predict serious consequences for the near future, and encourage the development of solutions for [...] Read more.
During the last three to four decades the prevalence of obesity and diabetes mellitus has greatly increased worldwide, including in the United States. Both the short- and long-term forecasts predict serious consequences for the near future, and encourage the development of solutions for the prevention and management of obesity and diabetes mellitus. Transient receptor potential (TRP) channels were identified in tissues and organs important for the control of whole body metabolism. A variety of TRP channels has been shown to play a role in the regulation of hormone release, energy expenditure, pancreatic function, and neurotransmitter release in control, obese and/or diabetic conditions. Moreover, dietary supplementation of natural ligands of TRP channels has been shown to have potential beneficial effects in obese and diabetic conditions. These findings raised the interest and likelihood for potential drug development. In this mini-review, we discuss possibilities for better management of obesity and diabetes mellitus based on TRP-dependent mechanisms. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
1042 KiB  
Review
Resiniferatoxin: The Evolution of the “Molecular Scalpel” for Chronic Pain Relief
by Dorothy Cimino Brown
Pharmaceuticals 2016, 9(3), 47; https://doi.org/10.3390/ph9030047 - 11 Aug 2016
Cited by 50 | Viewed by 8296
Abstract
Control of chronic pain is frequently inadequate or can be associated with debilitating side effects. Ablation of certain nociceptive neurons, while retaining all other sensory modalities and motor function, represents a new therapeutic approach to controlling severe pain while avoiding off-target side effects. [...] Read more.
Control of chronic pain is frequently inadequate or can be associated with debilitating side effects. Ablation of certain nociceptive neurons, while retaining all other sensory modalities and motor function, represents a new therapeutic approach to controlling severe pain while avoiding off-target side effects. transient receptor potential cation channel subfamily V member 1 (TRPV1) is a calcium permeable nonselective cation channel expressed on the peripheral and central terminals of small-diameter sensory neurons. Highly selective chemoablation of TRPV1-containing peripheral nerve endings, or the entire TRPV1-expressing neuron itself, can be used to control chronic pain. Administration of the potent TRPV1 agonist resiniferatoxin (RTX) to neuronal perikarya or nerve terminals induces calcium cytotoxicity and selective lesioning of the TRPV1-expressing nociceptive primary afferent population. This selective neuroablation has been coined “molecular neurosurgery” and has the advantage of sparing motor, proprioceptive, and other somatosensory functions that are so important for coordinated movement, performing activities of daily living, and maintaining quality of life. This review examines the mechanisms and preclinical data underlying the therapeutic use of RTX and examples of such use for the management of chronic pain in clinical veterinary and human pain states. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
►▼ Show Figures

Figure 1

1279 KiB  
Review
Differential Activation of TRP Channels in the Adult Rat Spinal Substantia Gelatinosa by Stereoisomers of Plant-Derived Chemicals
by Eiichi Kumamoto and Tsugumi Fujita
Pharmaceuticals 2016, 9(3), 46; https://doi.org/10.3390/ph9030046 - 28 Jul 2016
Cited by 15 | Viewed by 5484
Abstract
Activation of TRPV1, TRPA1 or TRPM8 channel expressed in the central terminal of dorsal root ganglion (DRG) neuron increases the spontaneous release of l-glutamate onto spinal dorsal horn lamina II (substantia gelatinosa; SG) neurons which play a pivotal role in regulating nociceptive [...] Read more.
Activation of TRPV1, TRPA1 or TRPM8 channel expressed in the central terminal of dorsal root ganglion (DRG) neuron increases the spontaneous release of l-glutamate onto spinal dorsal horn lamina II (substantia gelatinosa; SG) neurons which play a pivotal role in regulating nociceptive transmission. The TRP channels are activated by various plant-derived chemicals. Although stereoisomers activate or modulate ion channels in a distinct manner, this phenomenon is not fully addressed for TRP channels. By applying the whole-cell patch-clamp technique to SG neurons of adult rat spinal cord slices, we found out that all of plant-derived chemicals, carvacrol, thymol, carvone and cineole, increase the frequency of spontaneous excitatory postsynaptic current, a measure of the spontaneous release of l-glutamate from nerve terminals, by activating TRP channels. The presynaptic activities were different between stereoisomers (carvacrol and thymol; (−)-carvone and (+)-carvone; 1,8-cineole and 1,4-cineole) in the extent or the types of TRP channels activated, indicating that TRP channels in the SG are activated by stereoisomers in a distinct manner. This result could serve to know the properties of the central terminal TRP channels that are targets of drugs for alleviating pain. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
►▼ Show Figures

Figure 1

219 KiB  
Review
TRPV1 and TRPM8 in Treatment of Chronic Cough
by Eva Millqvist
Pharmaceuticals 2016, 9(3), 45; https://doi.org/10.3390/ph9030045 - 28 Jul 2016
Cited by 25 | Viewed by 7881
Abstract
Chronic cough is common in the population, and among some there is no evident medical explanation for the symptoms. Such a refractory or idiopathic cough is now often regarded as a neuropathic disease due to dysfunctional airway ion channels, though the knowledge in [...] Read more.
Chronic cough is common in the population, and among some there is no evident medical explanation for the symptoms. Such a refractory or idiopathic cough is now often regarded as a neuropathic disease due to dysfunctional airway ion channels, though the knowledge in this field is still limited. Persistent coughing and a cough reflex easily triggered by irritating stimuli, often in combination with perceived dyspnea, are characteristics of this disease. The patients have impaired quality of life and often reduced work capacity, followed by social and economic consequences. Despite the large number of individuals suffering from such a persisting cough, there is an unmet clinical need for effective cough medicines. The cough treatment available today often has little or no effect. Adverse effects mostly follow centrally acting cough drugs comprised of morphine and codeine, which demands the physician’s awareness. The possibilities of modulating airway transient receptor potential (TRP) ion channels may indicate new ways to treat the persistent cough “without a reason”. The TRP ion channel vanilloid 1 (TRPV1) and the TRP melastin 8 (TRPM8) appear as two candidates in the search for cough therapy, both as single targets and in reciprocal interaction. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
197 KiB  
Review
TRPM8 Puts the Chill on Prostate Cancer
by Guillaume P. Grolez and Dimitra Gkika
Pharmaceuticals 2016, 9(3), 44; https://doi.org/10.3390/ph9030044 - 09 Jul 2016
Cited by 29 | Viewed by 6090
Abstract
Prostate cancer (PCa) is one of the most frequently diagnosed cancers in developed countries. Several studies suggest that variations in calcium homeostasis are involved in carcinogenesis. Interestingly, (Transient Receptor Potential Melastatin member 8) TRPM8 calcium permeable channel expression is differentially regulated during prostate [...] Read more.
Prostate cancer (PCa) is one of the most frequently diagnosed cancers in developed countries. Several studies suggest that variations in calcium homeostasis are involved in carcinogenesis. Interestingly, (Transient Receptor Potential Melastatin member 8) TRPM8 calcium permeable channel expression is differentially regulated during prostate carcinogenesis, thereby suggesting a potential functional role for this channel in those cell processes, which are important for PCa evolution. Indeed, several studies have shown that TRPM8 plays a key role in processes such as the proliferation, viability and cell migration of PCa cells. Where cell migration is concerned, TRPM8 seems to have a protective anti-invasive effect and could be a particularly promising therapeutic target. The goal of this review is to inventory advances in understanding of the role of TRPM8 in the installation and progression of PCa. Full article
(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts)
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-16
Back to TopTop