scholarly journals Inherent P2X7 Receptors Regulate Macrophage Functions during Inflammatory Diseases

2021 ◽  
Vol 23 (1) ◽  
pp. 232
Author(s):  
Wenjing Ren ◽  
Patrizia Rubini ◽  
Yong Tang ◽  
Tobias Engel ◽  
Peter Illes
Keyword(s):  
Transient Receptor Potential ◽  
Inflammatory Diseases ◽  
Second Messengers ◽  
Receptor Potential ◽  
Mononuclear Phagocytes ◽  
P2x7 Receptors ◽  
Pannexin 1 ◽  
Therapeutic Consequences ◽  
High Concentrations ◽  
Transient Receptor

Macrophages are mononuclear phagocytes which derive either from blood-borne monocytes or reside as resident macrophages in peripheral (Kupffer cells of the liver, marginal zone macrophages of the spleen, alveolar macrophages of the lung) and central tissue (microglia). They occur as M1 (pro-inflammatory; classic) or M2 (anti-inflammatory; alternatively activated) phenotypes. Macrophages possess P2X7 receptors (Rs) which respond to high concentrations of extracellular ATP under pathological conditions by allowing the non-selective fluxes of cations (Na+, Ca2+, K+). Activation of P2X7Rs by still higher concentrations of ATP, especially after repetitive agonist application, leads to the opening of membrane pores permeable to ~900 Da molecules. For this effect an interaction of the P2X7R with a range of other membrane channels (e.g., P2X4R, transient receptor potential A1 [TRPA1], pannexin-1 hemichannel, ANO6 chloride channel) is required. Macrophage-localized P2X7Rs have to be co-activated with the lipopolysaccharide-sensitive toll-like receptor 4 (TLR4) in order to induce the formation of the inflammasome 3 (NLRP3), which then activates the pro-interleukin-1β (pro-IL-1β)-degrading caspase-1 to lead to IL-1β release. Moreover, inflammatory diseases (e.g., rheumatoid arthritis, Crohn’s disease, sepsis, etc.) are generated downstream of the P2X7R-induced upregulation of intracellular second messengers (e.g., phospholipase A2, p38 mitogen-activated kinase, and rho G proteins). In conclusion, P2X7Rs at macrophages appear to be important targets to preserve immune homeostasis with possible therapeutic consequences.

scholarly journals Developmental studies on the acquisition of perception conducting pathways via TRP channels in rat molar odontoblasts using immunohistochemistry and RT-qPCR

2019 ◽  
Vol 95 (2) ◽  
pp. 251-257
Author(s):  
Aoi Tanaka ◽  
Yoshiyuki Shibukawa ◽  
Masahito Yamamoto ◽  
Shinichi Abe ◽  
Hitoshi Yamamoto ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Quantitative Polymerase Chain Reaction ◽  
Receptor Potential ◽  
Nerve Fibers ◽  
Sensory Receptor ◽  
Developmental Studies ◽  
Pannexin 1 ◽  
Root Dentin ◽  
Transient Receptor

AbstractOdontoblasts act as dentin formation and sensory receptors. Recently, it was reported that transient receptor potential ankyrin (TRPA) 1, TRP vanilloid (TRPV) 4 and pannexin 1 (PANX-1) play important roles in odontoblast sensory reception. However, it is not known when odontoblasts begin to possess a sense reception function. The aim of this study was to clarify the development of odontoblasts as sense receptors. Sections of mandibular first molars from postnatal day (PN) 0 to PN12 Wistar rats were prepared for hematoxylin–eosin staining. Immunohistochemically, we used anti-dentin sialoprotein (DSP), anti-TRPA1, anti-TRPV4, anti-PANX-1, and anti-neurofilament (NF) antibodies. In addition, we investigated TRPA1 and TRPV4 expression by reverse transcriptional quantitative polymerase chain reaction (RT-qPCR). At PN0, undifferentiated odontoblasts showed no immunoreaction to anti-DSP, anti-TRPA1, anti-TRPV4, or anti-PANX-1 antibodies. However, immunopositive reactions of these antibodies increased during odontoblast differentiation at PN3 and PN6. An immunopositive reaction of the anti-NF antibody appeared in the odontoblast neighborhood at PN12, when the odontoblasts began to form root dentin, and this appeared later than that of the other antibodies. By RT-qPCR, expression of TRPA1 at PN6 was significantly lower than that at PN0 (p < 0.05) and PN3 (p < 0.01). Expression of TRPV4 at PN6 was significantly lower than that at PN0 (p < 0.01) and PN3 (p < 0.01). The results of this study suggest that odontoblasts may acquire sensory receptor function after beginning to form root dentin, when TRPA1, TRPV4, PANX-1 channels, and nerve fibers are completely formed.

scholarly journals Transforming TRP Channel Drug Discovery Using Medium-Throughput Electrophysiological Assays

2013 ◽  
Vol 19 (3) ◽  
pp. 468-477 ◽  
Author(s):  
Jean-Marie Chambard ◽  
Eric Tagat ◽  
Philippe Boudeau ◽  
Michel Partiseti
Keyword(s):  
Drug Discovery ◽  
Drug Target ◽  
Drug Targets ◽  
Transient Receptor Potential ◽  
Inflammatory Diseases ◽  
Receptor Potential ◽  
Target Class ◽  
Screening Assays ◽  
Transient Receptor ◽  
Almost All

Since the cloning of its first member in 1998, transient receptor potential (TRP) cation channels have become one of the most studied ion channel families in drug discovery. These channels, almost all calcium permeant, have been studied in many different (patho)-physiological and therapeutic areas as diverse as pain; neurodegenerative, cardiovascular, and inflammatory diseases; and cancer. At the same time, implementation of automated electrophysiology screening platforms has significantly increased the tractability of ion channels, mainly voltage gated, as drug targets. The work presented in this article shows the design and validation of TRP screening assays using the IonWorks Quattro platform (Molecular Devices, Sunnyvale, CA), allowing a significant increase in throughput to support drug discovery programs. This new player has a direct impact on resources and timelines by prioritizing potential candidates and reducing the number of molecules requiring final testing by manual patch-clamp, which is still today the gold standard technology for this challenging drug target class.

scholarly journals Transient Receptor Potential-Vanilloid (TRPV1-TRPV4) Channels in the Atlantic Salmon, Salmo salar. A Focus on the Pineal Gland and Melatonin Production

2022 ◽  
Vol 12 ◽  
Author(s):  
Laura Gabriela Nisembaum ◽  
Guillaume Loentgen ◽  
Thibaut L’Honoré ◽  
Patrick Martin ◽  
Charles-Hubert Paulin ◽  
...  
Keyword(s):  
Atlantic Salmon ◽  
Pineal Gland ◽  
Tissue Distribution ◽  
Salmo Salar ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
High Concentrations ◽  
Transient Receptor ◽  
Melatonin Production

Fish are ectotherm, which rely on the external temperature to regulate their internal body temperature, although some may perform partial endothermy. Together with photoperiod, temperature oscillations, contribute to synchronizing the daily and seasonal variations of fish metabolism, physiology and behavior. Recent studies are shedding light on the mechanisms of temperature sensing and behavioral thermoregulation in fish. In particular, the role of some members of the transient receptor potential channels (TRP) is being gradually unraveled. The present study in the migratory Atlantic salmon, Salmo salar, aims at identifying the tissue distribution and abundance in mRNA corresponding to the TRP of the vanilloid subfamilies, TRPV1 and TRPV4, and at characterizing their putative role in the control of the temperature-dependent modulation of melatonin production—the time-keeping hormone—by the pineal gland. In Salmo salar, TRPV1 and TRPV4 mRNA tissue distribution appeared ubiquitous; mRNA abundance varied as a function of the month investigated. In situ hybridization and immunohistochemistry indicated specific labeling located in the photoreceptor cells of the pineal gland and the retina. Additionally, TRPV analogs modulated the production of melatonin by isolated pineal glands in culture. The TRPV1 agonist induced an inhibitory response at high concentrations, while evoking a bell-shaped response (stimulatory at low, and inhibitory at high, concentrations) when added with an antagonist. The TRPV4 agonist was stimulatory at the highest concentration used. Altogether, the present results agree with the known widespread distribution and role of TRPV1 and TRPV4 channels, and with published data on trout (Oncorhynchus mykiss), leading to suggest these channels mediate the effects of temperature on S. salar pineal melatonin production. We discuss their involvement in controlling the timing of daily and seasonal events in this migratory species, in the context of an increasing warming of water temperatures.

scholarly journals Functional Importance of Transient Receptor Potential (TRP) Channels in Neurological Disorders

2021 ◽  
Vol 9 ◽  
Author(s):  
Kihwan Lee ◽  
Youn Yi Jo ◽  
Gehoon Chung ◽  
Jung Hoon Jung ◽  
Yong Ho Kim ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Protein Complexes ◽  
Transmembrane Protein ◽  
Second Messengers ◽  
Ion Homeostasis ◽  
Receptor Potential ◽  
Functional Roles ◽  
Transient Receptor

Transient receptor potential (TRP) channels are transmembrane protein complexes that play important roles in the physiology and pathophysiology of both the central nervous system (CNS) and the peripheral nerve system (PNS). TRP channels function as non-selective cation channels that are activated by several chemical, mechanical, and thermal stimuli as well as by pH, osmolarity, and several endogenous or exogenous ligands, second messengers, and signaling molecules. On the pathophysiological side, these channels have been shown to play essential roles in the reproductive system, kidney, pancreas, lung, bone, intestine, as well as in neuropathic pain in both the CNS and PNS. In this context, TRP channels have been implicated in several neurological disorders, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and epilepsy. Herein, we focus on the latest involvement of TRP channels, with a special emphasis on the recently identified functional roles of TRP channels in neurological disorders related to the disruption in calcium ion homeostasis.

Regulation of calcium signalling by adenine-based second messengers

2007 ◽  
Vol 35 (1) ◽  
pp. 109-114 ◽  
Author(s):  
R. Fliegert ◽  
A. Gasser ◽  
A.H. Guse
Keyword(s):  
Transient Receptor Potential ◽  
Second Messengers ◽  
Calcium Signalling ◽  
Receptor Potential ◽  
Cell Types ◽  
Cellular Systems ◽  
Membrane Receptors ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
Plasma Membrane Receptors

cADPR [cyclic ADPR (ADP-ribose)], NAADP (nicotinic acid–adenine dinucleotide phosphate) and ADPR belong to the family of adenine-containing second messengers. They are metabolically related and are all involved in the regulation of cellular Ca2+ homoeostasis. Activation of specific plasma membrane receptors is connected to cADPR formation in many cell types and tissues. In contrast receptor-mediated formation of NAADP and ADPR has been shown only in a few selected cellular systems. The intracellular Ca2+ channel triggered by cADPR is the RyR (ryanodine receptor); in the case of NAADP, both activation of RyR and a novel Ca2+ channel have been proposed. In contrast, ADPR opens the non-specific cation channel TRPM2 [TRP (transient receptor potential) melastatin 2] that belongs to the TRP family of ion channels.

scholarly journals Internal Ca2+ release in yeast is triggered by hypertonic shock and mediated by a TRP channel homologue

2002 ◽  
Vol 156 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Valérie Denis ◽  
Martha S. Cyert
Keyword(s):  
Mammalian Cells ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Second Messengers ◽  
Receptor Potential ◽  
Ip3 Receptors ◽  
Intracellular Compartments ◽  
No Signaling ◽  
Transient Receptor

Calcium ions, present inside all eukaryotic cells, are important second messengers in the transduction of biological signals. In mammalian cells, the release of Ca2+ from intracellular compartments is required for signaling and involves the regulated opening of ryanodine and inositol-1,4,5-trisphosphate (IP3) receptors. However, in budding yeast, no signaling pathway has been shown to involve Ca2+ release from internal stores, and no homologues of ryanodine or IP3 receptors exist in the genome. Here we show that hyperosmotic shock provokes a transient increase in cytosolic Ca2+ in vivo. Vacuolar Ca2+, which is the major intracellular Ca2+ store in yeast, is required for this response, whereas extracellular Ca2+ is not. We aimed to identify the channel responsible for this regulated vacuolar Ca2+ release. Here we report that Yvc1p, a vacuolar membrane protein with homology to transient receptor potential (TRP) channels, mediates the hyperosmolarity induced Ca2+ release. After this release, low cytosolic Ca2+ is restored and vacuolar Ca2+ is replenished through the activity of Vcx1p, a Ca2+/H+ exchanger. These studies reveal a novel mechanism of internal Ca2+ release and establish a new function for TRP channels.

scholarly journals A Novel Pro-Inflammatory Mechanosensing Pathway Orchestrated by the Disintegrin Metalloproteinase ADAM15 in Synovial Fibroblasts

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2705
Author(s):  
Tomasz Janczi ◽  
Florian Meier ◽  
Yuliya Fehrl ◽  
Raimund W. Kinne ◽  
Beate Böhm ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Transient Receptor Potential ◽  
Joint Destruction ◽  
Receptor Potential ◽  
Synovial Fibroblasts ◽  
Sirtuin 1 ◽  
Metabolic Energy ◽  
Transient Receptor Potential Vanilloid ◽  
Pannexin 1 ◽  
Transient Receptor

Mechanotransduction is elicited in cells upon the perception of physical forces transmitted via the extracellular matrix in their surroundings and results in signaling events that impact cellular functions. This physiological process is a prerequisite for maintaining the integrity of diarthrodial joints, while excessive loading is a factor promoting the inflammatory mechanisms of joint destruction. Here, we describe a mechanotransduction pathway in synovial fibroblasts (SF) derived from the synovial membrane of inflamed joints. The functionality of this pathway is completely lost in the absence of the disintegrin metalloproteinase ADAM15 strongly upregulated in SF. The mechanosignaling events involve the Ca2+-dependent activation of c-Jun-N-terminal kinases, the subsequent downregulation of long noncoding RNA HOTAIR, and upregulation of the metabolic energy sensor sirtuin-1. This afferent loop of the pathway is facilitated by ADAM15 via promoting the cell membrane density of the constitutively cycling mechanosensitive transient receptor potential vanilloid 4 calcium channels. In addition, ADAM15 reinforces the Src-mediated activation of pannexin-1 channels required for the enhanced release of ATP, a mediator of purinergic inflammation, which is increasingly produced upon sirtuin-1 induction.

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