Interactions Between Chemesthesis and Taste: Role of TRPA1 and TRPV1
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Oral Thermosensing by Murine Trigeminal Neurons: Modulation by Capsaicin, Menthol, and Mustard Oil
bioRxiv preprint doi: https://doi.org/10.1101/486480; this version posted December 4, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Oral thermosensing by murine trigeminal neurons: modulation by capsaicin, menthol, and mustard oil Sara C.M. Leijon1, Amanda F. Neves1, Sidney A. Simon2, Nirupa Chaudhari1,3, Stephen D. Roper1,3 1) Department of Physiology & Biophysics, Miller School of Medicine, University of Miami, Miami, FL, USA 2) Department of Neurobiology, Duke University, Durham, NC, USA 3) Department of Otolaryngology, Miller School of Medicine, University of Miami, and Program in Neuroscience, University of Miami, Miami, FL, USA Running title: Trigeminal orosensory responses in the mouse Key words: Trigeminal ganglion, sensory neurons, calcium imaging, thermosensation, chemesthesis Key points summary Orosensory thermal trigeminal afferent neurons respond to cool, warm, and nociceptive hot temperatures with the majority activated in the cool range. Many of these thermosensitive trigeminal orosensory afferent neurons also respond to capsaicin, menthol and/or mustard oil (allyl isothiocyanate, AITC) at concentrations found in foods and spices. There is significant but incomplete overlap between afferent trigeminal neurons that respond to heat and to the above chemesthetic compounds. Capsaicin sensitizes warm trigeminal thermoreceptors and orosensory nociceptors; menthol attenuates cool thermoresponses. 1 bioRxiv preprint doi: https://doi.org/10.1101/486480; this version posted December 4, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract When consumed with foods, mint, mustard and chili peppers generate pronounced oral thermosensations. -
Herbal Insecticide and Pesticide Save The
Sheaba Mariam Shaji et al., 2017/ Herbal insecticide and pesticide save the REVIEW ARTICLE International Research Journal of Pharmaceutical and Biosciences Pri -ISSN: 2394 - 5826 http://www.irjpbs.com e-ISSN: 2394 - 5834 Herbal Insecticide and Pesticide - Save the Life and Future Sheaba Mariam Shaji*, Shahana J, Ancy Thomas, Jiju V, Elessy Abraham Nazareth College of Pharmacy, Othera, Thiruvalla. Article info Abstract Insecticides provide many substantial benefits for farmers and consumers Article history: by controlling insects and preventing diseases, as well as increasing crop Received 02 APR 2017 Accepted 04 APR 2017 yield and keeping cost down; however, these potent chemicals have also put our health in great danger. The purpose of this is to identify the side effects of synthetic insecticides and the benefits of herbal insect repellents over them. The side effects of synthetic insecticides (organophosphate, organochlorine, carbamates etc) includes cancer, endocrine complications, infertility and sterility, brain damage, birth defects, respiratory disorders, organ failure, skin irritations etc. This can be avoided by the use of herbal insect repellents which includes peppermint, neem, pyrethrum, chrysanthemum catnip, quassia, tobacco etc. *Corresponding author: Key words: Insecticides, Preventing diseases, Natural. [email protected] Copyright 2017 irjpbs INTRODUCTION Herbal insecticides are biological agents that target certain unwanted living organism deter, incapacitates, kills, or otherwise discourages insects. They are a class of biocide. Herbal insecticidal method is a rapidly expanding field of agriculture, where natural agents, primarily parasitism and predators are used to control an insect that has been causing economic harm to human interests. These methods can be alternatives or supplements to conventional pest control methods such as synthetic pesticides. -
More Than Smell. COVID-19 Is Associated with Severe Impairment
medRxiv preprint doi: https://doi.org/10.1101/2020.05.04.20090902.this version posted May 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license . 1 More than smell – COVID-19 is associated with severe impairment of smell, taste, and chemesthesis By-line Authors: Valentina Parma1*, Kathrin Ohla2*, Maria G. Veldhuizen3*, Masha Y Niv4, Christine E Kelly5, Alyssa J. Bakke6, Keiland W. Cooper7, Cédric Bouysset8, Nicola Pirastu9, Michele Dibattista10, RishemJit Kaur11, Marco Tullio Liuzza12, Marta Y. Pepino13, Veronika Schöpf14, Veronica Pereda- Loth15, Shannon B Olsson16, Richard C Gerkin17, Paloma Rohlfs Domínguez18, Javier Albayay19, Michael C. Farruggia20, Surabhi Bhutani21, Alexander W. FJaeldstad22, Ritesh Kumar23, Anna Menini24, Moustafa Bensafi25, Mari Sandell26, Iordanis Konstantinidis27, Antonella Di Pizio28, Federica Genovese29, Lina Öztürk30, Thierry Thomas-Danguin31, Johannes Frasnelli32, Sanne Boesveldt33, Özlem Saatci34, Luis R. Saraiva35, Cailu Lin29, Jérôme Golebiowski36, Liang-Dar Hwang37, Mehmet Hakan Ozdener29, Maria Dolors Guàrdia38, Christophe Laudamiel39, Marina Ritchie40, Jan Havlícek41, Denis Pierron42, Eugeni Roura43, Marta Navarro43, Alissa A. Nolden44, Juyun Lim45, KL Whitcroft46, Lauren R Colquitt29, Camille Ferdenzi47, Evelyn V Brindha48, Aytug Altundag49, Alberto Macchi50, Alexia Nunez-Parra51, Zara M. Patel52, Sébastien Fiorucci36, Carl M Philpott53, Barry C. Smith54, Johan N. Lundström55, Carla Mucignat56, Jane K. Parker57, Mirjam van den Brink58, Michael Schmuker59, Florian Ph.S Fischmeister60, Thomas Heinbockel61, Vonnie D.C. Shields62, Farhoud FaraJi63, Enrique Santamaría64, William E.A. Fredborg65, Gabriella Morini66, Jonas K. Olofsson65, Maryam Jalessi67, Noam Karni68, Anna D’Errico69, Rafieh Alizadeh70, Robert Pellegrino71, Pablo Meyer72, Caroline Huart73, Ben Chen74, Graciela M. -
Transient Receptor Potential Channel Promiscuity Frustrates Constellation
the sole sensor responsible for noxious cold responses in M+A+ LETTER neurons (1). However, TRPA1 is also activated by cooling and underlies at least part of the noxious cold responsiveness of Transient receptor potential channel AITC-sensitive neurons (3). Third, the authors used nicardipine 2+ promiscuity frustrates to selectively inhibit CaV1-type voltage-gated Ca channels (1). However, several dihydropyridines, including nicardipine, also constellation pharmacology act as TRPA1 agonists (4). These considerations led us to propose an alternative Sensory neurons from the trigeminal and dorsal root ganglia molecular interpretation of the difference between M+A− (DRG) have nerve endings in the skin and mucosa, where they and M+A+ neurons, which is in much better agreement with detect environmental stimuli and convey this information to published work. In accord with the authors, we conclude that the central nervous system. Several members of the transient M+A− neurons express TRPM8 but lack expression of receptor potential (TRP) superfamily of ion channels act as TRPA1. In contrast to the authors, we propose that M+A+ prime molecular sensors for thermal and chemical stimuli in neurons express TRPA1 as the prime cold and menthol these sensory neurons. However, it is incompletely understood sensor (2, 3). This interpretation is consistent with published how TRP channel expression and modulation affect the stimulus observations that menthol responses in M+A− but not in sensitivities of distinct neuronal subtypes. M+A+ neurons are inhibited by TRPM8 antagonists (5) In a recent article, Teichert et al. (1) described a “constellation and that TRPA1-mediated responses to cold in neurons are pharmacology approach” to identify and characterize subtypes characterized by a higher (colder) threshold (3). -
Chapter Four – TRPA1 Channels: Chemical and Temperature Sensitivity
CHAPTER FOUR TRPA1 Channels: Chemical and Temperature Sensitivity Willem J. Laursen1,2, Sviatoslav N. Bagriantsev1,* and Elena O. Gracheva1,2,* 1Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA 2Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT, USA *Corresponding author: E-mail: [email protected], [email protected] Contents 1. Introduction 90 2. Activation and Regulation of TRPA1 by Chemical Compounds 91 2.1 Chemical activation of TRPA1 by covalent modification 91 2.2 Noncovalent activation of TRPA1 97 2.3 Receptor-operated activation of TRPA1 99 3. Temperature Sensitivity of TRPA1 101 3.1 TRPA1 in mammals 101 3.2 TRPA1 in insects and worms 103 3.3 TRPA1 in fish, birds, reptiles, and amphibians 103 3.4 TRPA1: Molecular mechanism of temperature sensitivity 104 Acknowledgments 107 References 107 Abstract Transient receptor potential ankyrin 1 (TRPA1) is a polymodal excitatory ion channel found in sensory neurons of different organisms, ranging from worms to humans. Since its discovery as an uncharacterized transmembrane protein in human fibroblasts, TRPA1 has become one of the most intensively studied ion channels. Its function has been linked to regulation of heat and cold perception, mechanosensitivity, hearing, inflam- mation, pain, circadian rhythms, chemoreception, and other processes. Some of these proposed functions remain controversial, while others have gathered considerable experimental support. A truly polymodal ion channel, TRPA1 is activated by various stimuli, including electrophilic chemicals, oxygen, temperature, and mechanical force, yet the molecular mechanism of TRPA1 gating remains obscure. In this review, we discuss recent advances in the understanding of TRPA1 physiology, pharmacology, and molecular function. -
The Role of Pain Receptors in the Main Symptoms of Covid-19 and How Diet Can Be a Therapy
Internal Medicine: Open Access Review Article The Role of Pain Receptors in the Main Symptoms of Covid-19 and How Diet Can Be a Therapy Francesco Amato1*, Erminia Gilda Morrone2 1UOC Pain Therapy and CP Hospital, Cosenza, Italy; 2Association Center for Pain Therapy Studies, Cosenza, Italy ABSTRACT It is estimated that 80% of SARS-CoV-2 patients have olfactory disturbances and many also have dysgeusia or ageusia (an interruption or loss of taste, respectively) or changes in chemesthesis, the ability to perceive irritants by TRP receptors. Anosmia (loss of sense of smell) and dysgeusia been termed 'sentinel symptoms'. Anosmia and ageusia represent a real health risk and can also cause nutritional deficits'. Infection with SARS-CoV-2 in the oral cavity could cause changes in the production or quality of saliva, contributing to the symptoms of taste loss. Since the activation of TRPs by Reactive Oxygen Species (ROS) contributes to inflammation and pain, research is focusing on several biological mediators related to TRPs and oxidative radicals that could help the development of treatments for pain itself and some COVID related symptoms. Recent studies have found that Nuclear Factor Erythroid-Related Factor 2 (NRF2) is a transcription factor that regulates cellular defence against toxic and oxidative insults. Compounds that can activate or induce NRF2 include garlic H2S polysulphides, cinnaldehyde in cinnamon, polyphenols in green tea, curcumin, a polyphenolic compound found in curcuma, piperine, an alkaloid found in black pepper, and glucoraphanin found in broccoli. In addition, there is a substantial electrophilic interaction between NRF2, TRPA1 and TPV1 that results in their desensitisation. -
TRPM8 Channels and Dry Eye
UC Berkeley UC Berkeley Previously Published Works Title TRPM8 Channels and Dry Eye. Permalink https://escholarship.org/uc/item/2gz2d8s3 Journal Pharmaceuticals (Basel, Switzerland), 11(4) ISSN 1424-8247 Authors Yang, Jee Myung Wei, Edward T Kim, Seong Jin et al. Publication Date 2018-11-15 DOI 10.3390/ph11040125 Peer reviewed eScholarship.org Powered by the California Digital Library University of California pharmaceuticals Review TRPM8 Channels and Dry Eye Jee Myung Yang 1,2 , Edward T. Wei 3, Seong Jin Kim 4 and Kyung Chul Yoon 1,* 1 Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwangju 61469, Korea; [email protected] 2 Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea 3 School of Public Health, University of California, Berkeley, CA 94720, USA; [email protected] 4 Department of Dermatology, Chonnam National University Medical School and Hospital, Gwangju 61469, Korea; [email protected] * Correspondence: [email protected] Received: 17 September 2018; Accepted: 12 November 2018; Published: 15 November 2018 Abstract: Transient receptor potential (TRP) channels transduce signals of chemical irritation and temperature change from the ocular surface to the brain. Dry eye disease (DED) is a multifactorial disorder wherein the eyes react to trivial stimuli with abnormal sensations, such as dryness, blurring, presence of foreign body, discomfort, irritation, and pain. There is increasing evidence of TRP channel dysfunction (i.e., TRPV1 and TRPM8) in DED pathophysiology. Here, we review some of this literature and discuss one strategy on how to manage DED using a TRPM8 agonist. -
GIANT ULLEUNG CELERY Stephen Barstow1, Malvik, March 2020
GIANT ULLEUNG CELERY 1 Stephen Barstow , Malvik, March 2020 Scientific name: Dystaenia takesimana Carrot family (Apiaceae) English: Seombadi, Sobadi, Dwaejipul, giant Ulleung celery, Korean pig-plant, wild celery, giant Korean celery Korean: 섬바디, 드와지풀 Norwegian: Ulleung kjempeselleri Swedish: Ullungloka, Vulkanloka The genus Dystaenia belongs to the carrot family or umbellifers (Apiaceae) and consists of two perennial species, one is a Japanese endemic (Dystaenia ibukiensis), and the other is endemic to a small island, Ulleung-do in Korea (Dystaenia takesimana). Genetic analysis (Pfosser et al., 2005) suggests that the larger D. takesimana evolved from D. ibukiensis rather than vice versa. The specific epithet takesimana is according to one reference to Takeshima Islet, which is disputed with the Japanese. Campanula takesimana is apparently found there. However, Takeshima island is also an alternative name for Ulleung-do, so this may be a misunderstanding. That Ulleung-do is Takeshima is confirmed on the following web site from the Oki Islands off Japan http://www.oki-geopark.jp/en/flowers-calendar/summer where it is stated that Dystaenia takesimana is also found there and is critically endangered: “This plant was designated as Cultural Property of Ama Town in 2012. It has only been discovered on the two isolated islands of Ama Town of the Oki Islands (Nakanoshima Island) and Ulleung-do Island of South Korea. It can be seen on the Akiya Coast in Nakanoshima Island. It is called Takeshima- shishiudo, as Ulleung-do was referred to as Takeshima” (see the map in Figure 1 for places mentioned here). Ulleung-do is a rocky steep-sided volcanic island some 120 km east of the coast of South Korea, the highest peak reaching 984m. -
Does Serotonin Deficiency Lead to Anosmia, Ageusia, Dysfunctional Chemesthesis and Increased Severity of Illness in COVID-19?
Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19? Amarnath Sen 40 Jadunath Sarbovouma Lane, Kolkata 700035, India, E-mail: [email protected] ABSTRACT Anosmia, ageusia and impaired chemesthetic sensations are quite common in coronavirus patients. Different mechanisms have been proposed to explain the anosmia and ageusia in COVID-19, though for reversible anosmia and ageusia, which are resolved quickly, the proposed mechanisms seem to be incomplete. In addition, the reason behind the impaired chemesthetic sensations in some coronavirus patients remains unknown. It is proposed that coronavirus patients suffer from depletion of tryptophan (an essential amino acid), as ACE2, a key element in the process of absorption of tryptophan from the food, is significantly reduced due to the attack of coronavirus, which use ACE2 as the receptor for its entry into the host cells. The depletion of tryptophan should lead to a deficit of serotonin (5-HT) in SARS-COV- 2 patients because tryptophan is the precursor in the synthesis of 5-HT. Such 5-HT deficiency can give rise to anosmia, ageusia and dysfunctional chemesthesis in COVID-19, given the fact that 5-HT is an important neuromodulator in the olfactory neurons and taste receptor cells and 5-HT also enhances the nociceptor activity of transient receptor potential channels (TRP channels) responsible for the chemesthetic sensations. In addition, 5-HT deficiency is expected to worsen silent hypoxemia and depress hypoxic pulmonary vasoconstriction (a protective reflex) leading to an increased severity of the disease and poor outcome. Melatonin, a potential adjuvant in the treatment of COVID-19, which can tone down cytokine storm, is produced from 5-HT and is expected to decrease due to the deficit of 5-HT in the coronavirus patients. -
Investigational Drugs in Early Phase Clinical Trials Targeting Thermotransient Receptor Potential (Thermotrp) Channels
Expert Opinion on Investigational Drugs ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/ieid20 Investigational drugs in early phase clinical trials targeting thermotransient receptor potential (thermoTRP) channels Asia Fernández-Carvajal , Rosario González-Muñiz , Gregorio Fernández- Ballester & Antonio Ferrer-Montiel To cite this article: Asia Fernández-Carvajal , Rosario González-Muñiz , Gregorio Fernández- Ballester & Antonio Ferrer-Montiel (2020): Investigational drugs in early phase clinical trials targeting thermotransient receptor potential (thermoTRP) channels, Expert Opinion on Investigational Drugs, DOI: 10.1080/13543784.2020.1825680 To link to this article: https://doi.org/10.1080/13543784.2020.1825680 Published online: 29 Sep 2020. Submit your article to this journal Article views: 31 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=ieid20 EXPERT OPINION ON INVESTIGATIONAL DRUGS https://doi.org/10.1080/13543784.2020.1825680 REVIEW Investigational drugs in early phase clinical trials targeting thermotransient receptor potential (thermoTRP) channels Asia Fernández-Carvajala, Rosario González-Muñizb, Gregorio Fernández-Ballestera and Antonio Ferrer-Montiela aInstituto De Investigación, Desarrollo E Innovación En Biotecnología Sanitaria De Elche (Idibe), Universitas Miguel Hernández, Alicante, Spain; bInstituto De Química Médica, CSIC, Madrid, Spain ABSTRACT ARTICLE HISTORY Introduction: Thermo transient receptor potential (thermoTRP) channels are some of the most inten Received 15 June 2020 sely pursued therapeutic targets of the past decade. They are considered promising targets of numer Accepted 15 September ous diseases including chronic pain and cancer. Modulators of these proteins, in particular TRPV1-4, 2020 TRPM8 and TRPA1, have reached clinical development, but none has been approved for clinical practice KEYWORDS yet. -
New Natural Agonists of the Transient Receptor Potential Ankyrin 1 (TRPA1
www.nature.com/scientificreports OPEN New natural agonists of the transient receptor potential Ankyrin 1 (TRPA1) channel Coline Legrand, Jenny Meylan Merlini, Carole de Senarclens‑Bezençon & Stéphanie Michlig* The transient receptor potential (TRP) channels family are cationic channels involved in various physiological processes as pain, infammation, metabolism, swallowing function, gut motility, thermoregulation or adipogenesis. In the oral cavity, TRP channels are involved in chemesthesis, the sensory chemical transduction of spicy ingredients. Among them, TRPA1 is activated by natural molecules producing pungent, tingling or irritating sensations during their consumption. TRPA1 can be activated by diferent chemicals found in plants or spices such as the electrophiles isothiocyanates, thiosulfnates or unsaturated aldehydes. TRPA1 has been as well associated to various physiological mechanisms like gut motility, infammation or pain. Cinnamaldehyde, its well known potent agonist from cinnamon, is reported to impact metabolism and exert anti-obesity and anti-hyperglycemic efects. Recently, a structurally similar molecule to cinnamaldehyde, cuminaldehyde was shown to possess anti-obesity and anti-hyperglycemic efect as well. We hypothesized that both cinnamaldehyde and cuminaldehyde might exert this metabolic efects through TRPA1 activation and evaluated the impact of cuminaldehyde on TRPA1. The results presented here show that cuminaldehyde activates TRPA1 as well. Additionally, a new natural agonist of TRPA1, tiglic aldehyde, was identifed -
Macromolecular Assembly of Polycystin-2 Intracytosolic C-Terminal Domain
Macromolecular assembly of polycystin-2 intracytosolic C-terminal domain Frederico M. Ferreiraa,b,1, Leandro C. Oliveirac, Gregory G. Germinod, José N. Onuchicc,1, and Luiz F. Onuchica,1 aDivision of Nephrology, University of São Paulo School of Medicine, 01246-903, São Paulo, Brazil; bLaboratory of Immunology, Heart Institute, University of São Paulo School of Medicine, 05403-900, São Paulo, Brazil; cCenter for Theoretical Biological Physics, University of California at San Diego, La Jolla, CA 92093; dNational Institute of Diabetes, Digestive, and Kidney Diseases, Bethesda, MD 20892-2560 Contributed by José N. Onuchic, April 28, 2011 (sent for review March 20, 2011) Mutations in PKD2 are responsible for approximately 15% of the In spite of the aforementioned information and insights, the autosomal dominant polycystic kidney disease cases. This gene macromolecular assembly of PC2t homooligomer continued to encodes polycystin-2, a calcium-permeable cation channel whose be an open question. In the current work, we present the most C-terminal intracytosolic tail (PC2t) plays an important role in its comprehensive set of analyses yet performed and that show interaction with a number of different proteins. In the present PC2t forms a homotetrameric oligomer. We have proposed a study, we have comprehensively evaluated the macromolecular PC2 C-terminal domain delimitation and submitted it to a range assembly of PC2t homooligomer using a series of biophysical of biochemical and biophysical evaluations, including chemical and biochemical analyses. Our studies, based on a new delimitation cross-linking, dynamic light scattering (DLS), circular dichroism of PC2t, have revealed that it is capable of assembling as a homo- (CD) and small angle X-ray scattering (SAXS) analyses.