scholarly journals Role of TRP Channels in Shaping the Gut Microbiome

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 753 ◽  
Author(s):  
Ravinder Nagpal ◽  
Santosh Kumar Mishra ◽  
Gagan Deep ◽  
Hariom Yadav
Keyword(s):  
Gut Microbiome ◽  
Transient Receptor Potential ◽  
Fatty Acid Biosynthesis ◽  
Trp Channels ◽  
Receptor Potential ◽  
Trp Channel ◽  
Double Knockout ◽  
Therapeutic Modalities ◽  
Trpv1 Channels ◽  
Noxious Chemicals

Transient receptor potential (TRP) channel family proteins are sensors for pain, which sense a variety of thermal and noxious chemicals. Sensory neurons innervating the gut abundantly express TRPA1 and TRPV1 channels and are in close proximity of gut microbes. Emerging evidence indicates a bi-directional gut–brain cross-talk in several entero-neuronal pathologies; however, the direct evidence of TRP channels interacting with gut microbial populations is lacking. Herein, we examine whether and how the knockout (KO) of TRPA1 and TRPV1 channels individually or combined TRPA1/V1 double-knockout (dKO) impacts the gut microbiome in mice. We detect distinct microbiome clusters among the three KO mouse models versus wild-type (WT) mice. All three TRP-KO models have reduced microbial diversity, harbor higher abundance of Bacteroidetes, and a reduced proportion of Firmicutes. Specifically distinct arrays in the KO models are determined mainly by S24-7, Bacteroidaceae, Clostridiales, Prevotellaceae, Helicobacteriaceae, Rikenellaceae, and Ruminococcaceae. A1KO mice have lower Prevotella, Desulfovibrio, Bacteroides, Helicobacter and higher Rikenellaceae and Tenericutes; V1KO mice demonstrate higher Ruminococcaceae, Lachnospiraceae, Ruminococcus, Desulfovibrio and Mucispirillum; and A1V1dKO mice exhibit higher Bacteroidetes, Bacteroides and S24-7 and lower Firmicutes, Ruminococcaceae, Oscillospira, Lactobacillus and Sutterella abundance. Furthermore, the abundance of taxa involved in biosynthesis of lipids and primary and secondary bile acids is higher while that of fatty acid biosynthesis-associated taxa is lower in all KO groups. To our knowledge, this is the first study demonstrating distinct gut microbiome signatures in TRPA1, V1 and dKO models and should facilitate prospective studies exploring novel diagnostic/ therapeutic modalities regarding the pathophysiology of TRP channel proteins.

scholarly journals Role of TRP Channels in Shaping Gut Microbiome

2020 ◽  
Author(s):  
Ravinder Nagpal ◽  
Santosh Kumar Mishra ◽  
Gagan Deep ◽  
Hariom Yadav
Keyword(s):  
Gut Microbiome ◽  
Transient Receptor Potential ◽  
Fatty Acid Biosynthesis ◽  
Trp Channels ◽  
Receptor Potential ◽  
Trp Channel ◽  
Double Knockout ◽  
Therapeutic Modalities ◽  
Trpv1 Channels ◽  
Noxious Chemicals

Transient receptor potential (TRP) channel family proteins are sensors for pain, which sense variety of thermal and noxious chemicals. Sensory neurons innervating the gut abundantly express TRPA1 and TRPV1 channels and are in close proximity of gut microbes. Emerging evidence indicates a bi-directional gut-brain cross-talk in several entero-neuronal pathologies; however, the direct evidence of TRP channels interacting with gut microbial populations is lacking. Herein, we examine whether and how the knockout (KO) of TRPA1 and TRPV1 channels individually or combined TRPA1/V1 double-knockout (dKO) impacts the gut microbiome in mice. We detect distinct microbiome clusters among the three KO mouse models versus wild-type (WT) mice. All three TRP-KO models have reduced microbial diversity, harbor higher abundance of Bacteroidetes, and reduced proportion of Firmicutes. Specifically distinct arrays in the KO models are determined mainly by S24-7, Bacteroidaceae, Clostridiales, Prevotellaceae, Helicobacteriaceae, Rikenellaceae, and Ruminococcaceae. A1KO mice have lower Prevotella, Desulfovibrio, Bacteroides, Helicobacter and higher Rikenellaceae and Tenericutes; V1KO mice demonstrate higher Ruminococcaceae, Lachnospiraceae, Ruminococcus, Desulfovibrio and Mucispirillum; while A1V1dKO mice exhibit higher Bacteroidetes, Bacteroides and S24-7 and lower Firmicutes, Ruminococcaceae, Oscillospira, Lactobacillus and Sutterella abundance. Also, the abundance of taxa involved in biosynthesis of lipids and primary and secondary bile acids is higher while that of fatty acid biosynthesis-associated taxa is lower in all KO groups. To our knowledge, this is the first study demonstrating distinct gut microbiome signatures in TRPA1, V1 and dKO models and should facilitate prospective studies exploring novel diagnostic/ therapeutic modalities regarding the pathophysiology of TRP channel proteins.

scholarly journals TRP Channels as Sensors of Aldehyde and Oxidative Stress

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1401
Author(s):  
Katharina E. M. Hellenthal ◽  
Laura Brabenec ◽  
Eric R. Gross ◽  
Nana-Maria Wagner
Keyword(s):  
Lipid Peroxidation ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Treatment Options ◽  
Receptor Potential ◽  
The Body ◽  
Trp Channel ◽  
Alcoholic Beverages ◽  
Organ Injury ◽  
Transient Receptor

The transient receptor potential (TRP) cation channel superfamily comprises more than 50 channels that play crucial roles in physiological processes. TRP channels are responsive to several exogenous and endogenous biomolecules, with aldehydes emerging as a TRP channel trigger contributing to a cellular cascade that can lead to disease pathophysiology. The body is not only exposed to exogenous aldehydes via tobacco products or alcoholic beverages, but also to endogenous aldehydes triggered by lipid peroxidation. In response to lipid peroxidation from inflammation or organ injury, polyunsaturated fatty acids undergo lipid peroxidation to aldehydes, such as 4-hydroxynonenal. Reactive aldehydes activate TRP channels via aldehyde-induced protein adducts, leading to the release of pro-inflammatory mediators driving the pathophysiology caused by cellular injury, including inflammatory pain and organ reperfusion injury. Recent studies have outlined how aldehyde dehydrogenase 2 protects against aldehyde toxicity through the clearance of toxic aldehydes, indicating that targeting the endogenous aldehyde metabolism may represent a novel treatment strategy. An addition approach can involve targeting specific TRP channel regions to limit the triggering of a cellular cascade induced by aldehydes. In this review, we provide a comprehensive summary of aldehydes, TRP channels, and their interactions, as well as their role in pathological conditions and the different therapeutical treatment options.

scholarly journals TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain

2018 ◽  
Vol 115 (7) ◽  
pp. E1657-E1666 ◽  
Author(s):  
Miguel Ortíz-Rentería ◽  
Rebeca Juárez-Contreras ◽  
Ricardo González-Ramírez ◽  
León D. Islas ◽  
Félix Sierra-Ramírez ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Sigma 1 Receptor ◽  
Trpv1 Channels ◽  
Nociceptive Responses ◽  
Sigma 1 ◽  
Transient Receptor ◽  
Thermal Stimuli

The Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel is expressed in nociceptors where, when activated by chemical or thermal stimuli, it functions as an important transducer of painful and itch-related stimuli. Although the interaction of TRPV1 with proteins that regulate its function has been previously explored, their modulation by chaperones has not been elucidated, as is the case for other mammalian TRP channels. Here we show that TRPV1 physically interacts with the Sigma 1 Receptor (Sig-1R), a chaperone that binds progesterone, an antagonist of Sig-1R and an important neurosteroid associated to the modulation of pain. Antagonism of Sig-1R by progesterone results in the down-regulation of TRPV1 expression in the plasma membrane of sensory neurons and, consequently, a decrease in capsaicin-induced nociceptive responses. This is observed both in males treated with a synthetic antagonist of Sig-1R and in pregnant females where progesterone levels are elevated. This constitutes a previously undescribed mechanism by which TRPV1-dependent nociception and pain can be regulated.

scholarly journals The nonselective cation channel TRPV4 inhibits angiotensin II receptors

2020 ◽  
Vol 295 (29) ◽  
pp. 9986-9997
Author(s):  
Nicholas W. Zaccor ◽  
Charlotte J. Sumner ◽  
Solomon H. Snyder
Keyword(s):  
Angiotensin Ii ◽  
G Protein ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Trp Channel ◽  
Luciferase Assay ◽  
Transient Receptor Potential Vanilloid ◽  
Dependent Manner ◽  
Transient Receptor

G-protein–coupled receptors (GPCRs) are a ubiquitously expressed family of receptor proteins that regulate many physiological functions and other proteins. They act through two dissociable signaling pathways: the exchange of GDP to GTP by linked G-proteins and the recruitment of β-arrestins. GPCRs modulate several members of the transient receptor potential (TRP) channel family of nonselective cation channels. How TRP channels reciprocally regulate GPCR signaling is less well-explored. Here, using an array of biochemical approaches, including immunoprecipitation and fluorescence, calcium imaging, phosphate radiolabeling, and a β-arrestin–dependent luciferase assay, we characterize a GPCR–TRP channel pair, angiotensin II receptor type 1 (AT1R), and transient receptor potential vanilloid 4 (TRPV4), in primary murine choroid plexus epithelial cells and immortalized cell lines. We found that AT1R and TRPV4 are binding partners and that activation of AT1R by angiotensin II (ANGII) elicits β-arrestin–dependent inhibition and internalization of TRPV4. Activating TRPV4 with endogenous and synthetic agonists inhibited angiotensin II–mediated G-protein–associated second messenger accumulation, AT1R receptor phosphorylation, and β-arrestin recruitment. We also noted that TRPV4 inhibits AT1R phosphorylation by activating the calcium-activated phosphatase calcineurin in a Ca2+/calmodulin–dependent manner, preventing β-arrestin recruitment and receptor internalization. These findings suggest that when TRP channels and GPCRs are co-expressed in the same tissues, many of these channels can inhibit GPCR desensitization.

scholarly journals TRPV1 Inhibits the Ventilatory Response to Hypoxia in Adult Rats, but Not the CO2-Drive to Breathe

2019 ◽  
Vol 12 (1) ◽  
pp. 19 ◽  
Author(s):  
Luis Patrone ◽  
Jaime Duarte ◽  
Kênia Bícego ◽  
Alexandre Steiner ◽  
Andrej Romanovsky ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Ventilatory Response ◽  
Pulmonary Ventilation ◽  
Receptor Potential ◽  
Current Data ◽  
Adult Rats ◽  
Cardiorespiratory Control ◽  
Trpv1 Channels

Receptors of the transient receptor potential (TRP) channels superfamily are expressed in many tissues and have different physiological functions. However, there are few studies investigating the role of these channels in cardiorespiratory control in mammals. We assessed the role of central and peripheral TRPV1 receptors in the cardiorespiratory responses to hypoxia (10% O2) and hypercapnia (7% CO2) by measuring pulmonary ventilation ( V ˙ E ), heart rate (HR), mean arterial pressure (MAP) and body temperature (Tb) of male Wistar rats before and after intraperitoneal (AMG9810 [2.85 µg/kg, 1 mL/kg]) or intracebroventricular (AMG9810 [2.85 µg/kg, 1 µL] or AMG7905 [28.5 μg/kg, 1 µL]) injections of TRPV1 antagonists. Central or peripheral injection of TRPV1 antagonists did not change cardiorespiratory parameters or Tb during room air and hypercapnic conditions. However, the hypoxic ventilatory response was exaggerated by both central and peripheral injection of AMG9810. In addition, the peripheral antagonist blunted the drop in Tb induced by hypoxia. Therefore, the current data provide evidence that TRPV1 channels exert an inhibitory modulation on the hypoxic drive to breathe and stimulate the Tb reduction during hypoxia.

Intragastric administration of allyl isothiocyanate increases carbohydrate oxidation via TRPV1 but not TRPA1 in mice

2011 ◽  
Vol 300 (6) ◽  
pp. R1494-R1505 ◽  
Author(s):  
Noriyuki Mori ◽  
Fuminori Kawabata ◽  
Shigenobu Matsumura ◽  
Hiroshi Hosokawa ◽  
Shigeo Kobayashi ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Allyl Isothiocyanate ◽  
Carbohydrate Oxidation ◽  
Trp Channel ◽  
Ion Concentration ◽  
Intragastric Administration ◽  
Intracellular Calcium Ion ◽  
Transient Receptor

The transient receptor potential (TRP) channel family is composed of a wide variety of cation-permeable channels activated polymodally by various stimuli and is implicated in a variety of cellular functions. Recent investigations have revealed that activation of TRP channels is involved not only in nociception and thermosensation but also in thermoregulation and energy metabolism. We investigated the effect of intragastric administration of TRP channel agonists on changes in energy substrate utilization of mice. Intragastric administration of allyl isothiocyanate (AITC; a typical TRPA1 agonist) markedly increased carbohydrate oxidation but did not affect oxygen consumption. To examine whether TRP channels mediate this increase in carbohydrate oxidation, we used TRPA1 and TRPV1 knockout (KO) mice. Intragastric administration of AITC increased carbohydrate oxidation in TRPA1 KO mice but not in TRPV1 KO mice. Furthermore, AITC dose-dependently increased intracellular calcium ion concentration in cells expressing TRPV1. These findings suggest that AITC might activate TRPV1 and that AITC increased carbohydrate oxidation via TRPV1.

scholarly journals Expression profile of the transient receptor potential (TRP) family in neutrophil granulocytes: evidence for currents through long TRP channel 2 induced by ADP-ribose and NAD

2003 ◽  
Vol 371 (3) ◽  
pp. 1045-1053 ◽  
Author(s):  
Inka HEINER ◽  
Jörg EISFELD ◽  
Christian R. HALASZOVICH ◽  
Edith WEHAGE ◽  
Eberhard JÜNGLING ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Single Channel ◽  
Gradient Centrifugation ◽  
Receptor Potential ◽  
Vanilloid Receptor ◽  
Trp Channel ◽  
Human Neutrophils ◽  
Neutrophil Granulocytes ◽  
Transient Receptor

An early key event in the activation of neutrophil granulocytes is Ca2+ influx. Members of the transient receptor potential (TRP) channel family may be held responsible for this. The aim of the present study is to analyse the expression pattern of TRP mRNA and identify characteristic currents unambiguously attributable to particular TRP channels. mRNA was extracted from human neutrophils, isolated by gradient centrifugation and also by magnetically labelled CD15 antibodies. The presence of mRNA was demonstrated using reverse transcriptase–PCR in neutrophils (controlled to be CD5-negative) as well as in human leukaemic cell line 60 (HL-60) cells, for the following TRP species: the long TRPC2 (LTRPC2), the vanilloid receptor 1, the vanilloid receptor-like protein 1 and epithelial Ca2+ channels 1 and 2. TRPC6 was specific for neutrophils, whereas only in HL-60 cells were TRPC1, TRPC2, TRPC3, melastatin 1 and melastatin-related 1 found. Patch-clamp measurements in neutrophils revealed non-selective cation currents evoked by intracellular ADP-ribose and by NAD+. Both these modes of activation have been found to be characteristic of LTRPC2. Furthermore, single-channel activity was resolved in neutrophils and it was indistinguishable from that in LTRPC2-transfected HEK-293 cells. The results provide evidence that LTRPC2 in neutrophil granulocytes forms an entry pathway for Na+ and Ca2+, which is regulated by ADP-ribose and the redox state.

scholarly journals Transient receptor potential ion channel function in sensory transduction and cellular signaling cascades underlying visceral hypersensitivity

2017 ◽  
Vol 312 (6) ◽  
pp. G635-G648 ◽  
Author(s):  
Dafne Balemans ◽  
Guy E. Boeckxstaens ◽  
Karel Talavera ◽  
Mira M. Wouters
Keyword(s):  
Signaling Pathways ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Visceral Hypersensitivity ◽  
Sensory Transduction ◽  
Trp Channel ◽  
Visceral Afferents ◽  
Altered Expression ◽  
Transient Receptor

Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders including functional dyspepsia, irritable bowel syndrome, and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family. A variety of TRP channels are present in the gastrointestinal tract (TRPV1, TRPV3, TRPV4, TRPA1, TRPM2, TRPM5, and TRPM8), and modulation of their function by increased activation or sensitization (decreased activation threshold) or altered expression in visceral afferents have been reported in visceral hypersensitivity. TRP channels directly detect or transduce osmotic, mechanical, thermal, and chemosensory stimuli. In addition, pro-inflammatory mediators released in tissue damage or inflammation can activate receptors of the G protein-coupled receptor superfamily leading to TRP channel sensitization and activation, which amplify pain and neurogenic inflammation. In this review, we highlight the present knowledge on the functional roles of neuronal TRP channels in visceral hypersensitivity and discuss the signaling pathways that underlie TRP channel modulation. We propose that a better understanding of TRP channels and their modulators may facilitate the development of more selective and effective therapies to treat visceral hypersensitivity.

scholarly journals Evidence for Transient Receptor Potential (TRP) Channel Contribution to Arthritis Pain and Pathogenesis

2018 ◽  
Vol 11 (4) ◽  
pp. 105 ◽  
Author(s):  
Tabitha Galindo ◽  
Jose Reyna ◽  
Andy Weyer
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Targets ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Trp Channel ◽  
Potential Drug ◽  
Current State ◽  
Transient Receptor ◽  
Potential Drug Targets

Based on clinical and preclinical evidence, Transient Receptor Potential (TRP) channels have emerged as potential drug targets for the treatment of osteoarthritis, rheumatoid arthritis, and gout. This review summarizes the relevant data supporting a role for various TRP channels in arthritis pain and pathogenesis, as well as the current state of pharmacological efforts to ameliorate arthritis symptoms in patient populations.

scholarly journals Structure of the thermo-sensitive TRP channel TRP1 from the alga Chlamydomonas reinhardtii

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Luke L. McGoldrick ◽  
Appu K. Singh ◽  
Lusine Demirkhanyan ◽  
Ting-Yu Lin ◽  
Ryan G. Casner ◽  
...  
Keyword(s):  
Chlamydomonas Reinhardtii ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Membrane Lipid ◽  
Membrane Receptors ◽  
Trp Channel ◽  
Structural Framework ◽  
Trp Ion Channels ◽  
Transient Receptor

Abstract Algae produce the largest amount of oxygen on earth and are invaluable for human nutrition and biomedicine, as well as for the chemical industry, energy production and agriculture. The mechanisms by which algae can detect and respond to changes in their environments can rely on membrane receptors, including TRP ion channels. Here we present a 3.5-Å resolution cryo-EM structure of the transient receptor potential (TRP) channel crTRP1 from the alga Chlamydomonas reinhardtii that opens in response to increased temperature and is positively regulated by the membrane lipid PIP2. The structure of crTRP1 significantly deviates from the structures of other TRP channels and has a unique 2-fold symmetrical rose-shape architecture with elbow domains and ankyrin repeat domains submerged and dipping into the membrane, respectively. Our study provides a structure of a TRP channel from a micro-organism and a structural framework for better understanding algae biology and TRP channel evolution.

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