Publications by authors named "Makoto Tominaga"

We investigated whether an anti-inflammatory lipid metabolite named 5,6-DiHETE reduces vascular permeability by inhibiting TRPV4 channels in vivo. In wild-type (WT) mice, histamine-induced dye extravasation was reduced by pre-administration of 5,6-DiHETE. In TRPV4-deficient mice, extravasation and histamine-induced edema were already reduced, and 5,6-DiHETE had no additional effect.

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Somatosensory neurons can sense external temperature by converting sensation of temperature information to neural activity via afferent input to the central nervous system. Various populations of somatosensory neurons have specialized gene expression, including expression of thermosensitive transient receptor potential (TRP) ion channels. Thermosensitive TRP channels are responsible for thermal transduction at the peripheral ends of somatosensory neurons and can sense a wide range of temperatures.

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Transient Receptor Potential Vanilloid 1 (TRPV1) plays a central role in pain sensation and is thus an attractive pharmacological drug target. SAF312 is a potent, selective, and non-competitive antagonist of TRPV1 and shows promising potential in treating ocular surface pain. However, the precise mechanism by which SAF312 inhibits TRPV1 remains poorly understood.

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Thermoregulation is a fundamental mechanism for maintaining homeostasis in living organisms because temperature affects essentially all biochemical and physiological processes. Effector responses to internal and external temperature cues are critical for achieving effective thermoregulation by controlling heat production and dissipation. Thermoregulation can be classified as physiological, which is observed primarily in higher organisms (homeotherms), and behavioral, which manifests as crucial physiological functions that are conserved across many species.

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Reports indicate that an interaction between TRPV4 and anoctamin 1 (ANO1) could be widely involved in water efflux of exocrine glands, suggesting that the interaction could play a role in perspiration. In secretory cells of sweat glands present in mouse foot pads, TRPV4 clearly colocalized with cytokeratin 8, ANO1, and aquaporin-5 (AQP5). Mouse sweat glands showed TRPV4-dependent cytosolic Ca increases that were inhibited by menthol.

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Article Synopsis
  • * TRP channels are crucial non-selective cation channels involved in various physiological functions across different body tissues, with significant research beginning after the discovery of TRPV1 in 1997.
  • * The review focuses on recent insights into how ANO1 interacts with specific TRP channels (like TRPV4, TRPC6, TRPV3, TRPV1, and TRPC2) in multiple tissues, indicating that ANO1 may regulate functions via chloride ion movement in those areas.
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Recent insights reveal the significant role of TRPV3 in warmth sensation. A novel finding elucidated how thermosensation is affected by TRPV3 membrane abundance that is modulated by the transmembrane protein TMEM79. TRPV3 is a warmth-sensitive ion channel predominantly expressed in epithelial cells, particularly skin keratinocytes.

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The nonselective calcium-permeable Transient Receptor Potential Cation Channel Subfamily V Member4 (TRPV4) channel regulates various physiological activities. Dysfunction of TRPV4 is linked to many severe diseases, including edema, pain, gastrointestinal disorders, lung diseases, and inherited neurodegeneration. Emerging TRPV4 antagonists show potential clinical benefits.

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  • Langerhans cells (LCs) are important immune cells found in the skin and help fight infections.
  • This study looked at how LCs move and change shape when they are activated by a substance called LPS.
  • They discovered that LPS makes LCs stick more to a surface and changes their shape, but it also slows down how fast they can move, which can help them during inflammation.
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Animals must sense and acclimatize to environmental temperatures for survival, yet their thermosensing mechanisms other than transient receptor potential (TRP) channels remain poorly understood. We identify a trimeric G protein-coupled receptor (GPCR), SRH-40, which confers thermosensitivity in sensory neurons regulating temperature acclimatization in Caenorhabditis elegans. Systematic knockdown of 1000 GPCRs by RNAi reveals GPCRs involved in temperature acclimatization, among which srh-40 is highly expressed in the ADL sensory neuron, a temperature-responsive chemosensory neuron, where TRP channels act as accessorial thermoreceptors.

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There are a lot of temperature-sensitive proteins including transient receptor potential (TRP) channels. Some TRP channels are temperature receptors having specific activation temperatures in vitro that are within the physiological temperature range. Mice deficient in specific TRP channels show abnormal thermal behaviors, but the role of TRP channels in these behaviors is not fully understood.

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Transient receptor potential (TRP) channels are primary sensory molecules in animals and are involved in detecting a diverse range of physical and chemical cues in the environments. Considering the crucial role of TRPA1 channels in nocifensive behaviors and aversive responses across various insect species, activators of TRPA1 are promising candidates for insect pest control. In this study, we demonstrate that 2-methylthiazoline (2MT), an artificial volatile thiazoline compound originally identified as a stimulant for mouse TRPA1, can be utilized as a novel repellent for fruit flies, .

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TRPV3, a non-selective cation transient receptor potential (TRP) ion channel, is activated by warm temperatures. It is predominantly expressed in skin keratinocytes, and participates in various somatic processes. Previous studies have reported that thermosensation in mice lacking TRPV3 was impaired.

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Transient receptor potential (TRP) channels play a significant role in taste perception. TRP ankyrin 1 (TRPA1) is present in the afferent sensory neurons and is activated by food-derived ingredients, such as Japanese horseradish, cinnamon, and garlic. The present study aimed to investigate the expression of TRPA1 in taste buds, and determine its functional roles in taste perception using TRPA1-deficient mice.

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Bitterness is an important physiological function in the defense responses to avoid toxic foods. The taste receptor 2 family is well known to mediate bitter taste perception in Type II taste cells. Here, we report that the polycystic kidney disease 2-like 1 (PKD2L1) channel is a novel sensor for the bitter aftertaste in Type III taste cells.

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The skin is a protective interface between the internal organs and environment and functions not only as a physical barrier but also as an immune organ. However, the immune system in the skin is not fully understood. A member of the thermo-sensitive transient receptor potential (TRP) channel family, TRPM4, which acts as a regulatory receptor in immune cells, was recently reported to be expressed in human skin and keratinocytes.

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Transient receptor potential vanilloid 3 (TRPV3) belongs to the TRP ion channel super family and functions as a nonselective cation channel that is highly permeable to calcium. This channel is strongly expressed in skin keratinocytes and is involved in warmth sensation, itch, wound healing and secretion of several cytokines. Previous studies showed that anoctamin1 (ANO1), a calcium-activated chloride channel, was activated by calcium influx through TRPV1, TRPV4 or TRPA1 and that these channel interactions were important for TRP channel-mediated physiological functions.

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Article Synopsis
  • The study focuses on how TRPV4, a calcium-permeable channel activated at moderate temperatures, influences macrophage function in skin immune diseases like atopic dermatitis.
  • It was found that activating TRPV4 can inhibit NF-κB signaling and reduce the production of IL-1β, a pro-inflammatory cytokine, in human macrophages and monocytes.
  • Additionally, the research suggests that TRPV4 activation may prevent the inflammatory differentiation of certain macrophages, indicating its potential as a therapeutic target for managing inflammation in skin diseases.
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The taste is biologically of intrinsic importance. It almost momentarily perceives environmental stimuli for better survival. In the early 2000s, research into taste reception was greatly developed with discovery of the receptors.

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  • The study investigated how cool temperatures affect colonic peristalsis, focusing on a specific ion channel (TRPM8) linked to temperature sensitivity.
  • In a trial with 94 patients undergoing colonoscopy, those exposed to mildly cool water showed a higher rate of reduced peristalsis compared to the control group, indicating an antispasmodic effect.
  • Results in rodent models confirmed the significant decrease in peristalsis with cool water, and TRPM8-deficient mice did not experience the same reduction, suggesting TRPM8's crucial role in this process.
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phototransduction is a model for signaling cascades that culminate in the activation of transient receptor potential (TRP) cation channels. TRP and TRPL are the canonical TRP (TRPC) channels that are regulated by light stimulation of rhodopsin and engagement of Gα and phospholipase Cβ (PLC). Lipid metabolite(s) generated downstream of PLC are essential for the activation of the TRPC channels in photoreceptor cells.

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The transient receptor potential melastatin type 2 (TRPM2) channel is a non-selective cation channel that has high Ca permeability. TRPM2 is sensitive to warm temperatures and is expressed in cells and tissues that are maintained at core body temperature. TRPM2 activity is also regulated by endogenous factors including redox signalling, cytosolic Ca and adenosine diphosphate ribose.

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Environmental temperature is a critical factor for all forms of life, and thermal tolerance defines the habitats utilized by a species. Moreover, the evolutionary tuning of thermal perception can also play a key role in habitat selection. Yet, the relative importance of thermal tolerance and perception in environmental adaptation remains poorly understood.

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Animals detect heat using thermosensitive transient receptor potential (TRP) channels. In insects, these include TRP ankyrin 1 (TRPA1), which in mosquitoes is crucial for noxious heat avoidance and thus is an appealing pest control target. However, the molecular basis for heat-evoked activation has not been fully elucidated, impeding both studies of the molecular evolution of temperature sensitivity and rational design of inhibitors.

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