Dissertations / Theses on the topic 'Transient receptor potential receptors'
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Liapi, Anastasia. "Cloning of the vanilloid-like receptor VR-L and investigation of its interaction with members of the transient receptor potential family of receptors." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270624.
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Stokes, Alexander James. "Regulatory interactions of transient receptor potential channels." Thesis, University of Warwick, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418114.
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Abe, Junji. "Localization and desensitization of transient receptor potential M8." 京都大学 (Kyoto University), 2007. http://hdl.handle.net/2433/135954.
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Kim, Ju Young. "M1 muscarinic acetylcholine receptor regulation of endogenous transient receptor potential-canonical, subtype 6 (TRPC6) channels." Connect to resource, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1117570788.
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Thesis (Ph. D.)--Ohio State University, 2005.Title from first page of PDF file. Document formatted into pages; contains xviii, 178 p.; also includes graphics. Includes bibliographical references (p. 163-178). Available online via OhioLINK's ETD Center
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Clark, Natalie Carol. "Evaluation of the roles of adrenomedullin1 (AM1) and transient receptor potential vanilloid1 (TRPV1) receptors in an LPS model of sepsis." Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434778.
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Friedrich, Olaf. "Biochemische und funktionelle Charakterisierung des potentiellen Calciumionenkanalproteins Maus-transient-receptor-Potential-1[beta] [Maus-transient-receptor-Potential-1beta] (mTRP1[beta] [(mTRP1beta)]." [S.l. : s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=963048163.
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Cao, De-Shou. "Role of transient receptor potential (TRP) channels in nociception /." Available to subscribers only, 2009. http://proquest.umi.com/pqdweb?did=1967913291&sid=2&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Cao, Deshou. "Role of Transient Receptor Potential (TRP) Channels in Nociception." OpenSIUC, 2009. https://opensiuc.lib.siu.edu/dissertations/71.
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Transient receptor potential (TRP) channels play an important role in sensory and nonsensory functions. TRPVanilloid 1 and TRPVanilloid 4 are proposed to be involved in inflammation-induced pain. TRPV1 is extensively studied and it is specifically involved in inflammatory thermal hypersensitivity. Mechanical hypersensitivity is one of the significant components of nociception. Several receptors have been proposed to underlie mechanosensation. The molecular entities responsible for mechanosensation are not fully understood. In this study, I have characterized the properties of TRPV4, a putative mechanosensitive ion channel expressed in dorsal root ganglion (DRG) neurons and nonsensory tissues. First, I have investigated the expression and function of TRPV4 and TRPV1 in the DRG neuronal cell bodies as well as their central terminals and determined the modulation by protein kinase C (PKC). Both TRPV4 and TRPV1 are expressed in DRG and laminae I and II of the spinal dorsal horn (DH). Ca2+ fluorescence imaging and whole-cell patch-clamp experiments showed that both capsaicin-induced TRPV1 response and 4alpha-phorbol 12, 13-didecanoate (4alpha-PDD)-induced TRPV4 response were observed in a proportion of the same DRG neurons, suggesting their co-expression. Incubation of DRG neurons with phorbol 12, 13-dibutyrate (PDBu), a PKC activator, resulted in a significantly greater potentiation of TRPV4 currents than TRPV1 currents. In HEK cells heterologously expressing TRPV4, PDBu potentiated TRPV4-mediated single-channel current activity. In patch-clamped DH neurons, the application of 4alpha-PDD at the first sensory synapse increased the frequency but not the amplitude of the miniature excitatory postsynaptic currents (mEPSCs), suggesting a presynaptic locus of action. 4alpha-PDD-induced increase in the frequency of mEPSC was further facilitated by PDBu. These results suggest that TRPV4 in the central terminals modulates synaptic transmission and is regulated by PKC. Second, I have studied the mechanosensitivity of TRPV4 in cell-attached patches by applying direct mechanical force via the patch pipette. In TRPV4 expressing HEK cells, the application of negative pressure evoked single-channel current activity in a reversible manner and the channel activity was enhanced after incubation with PDBu. TRPV4 has been shown to be activated by hypotonicity. Here I show that negative pressure exaggerated hypotonicity-induced single-channel current activity. However, in similar experimental conditions, cells expressing TRPV1 did not respond to mechanical force. TRP channels are also expressed in non-sensory regions and the role of these channels is not fully understood. Both TRPV4 and TRPV1 are expressed in the hippocampus. Using whole-cell patch-clamp techniques, I have found that 4alpha-PDD increased the frequency, but not the amplitude of mEPSCs in cultured hippocampal neurons, suggesting a presynaptic site of action. Interestingly, the application of capsaicin had no effect on synaptic transmission in hippocampal neuronal cultures. Finally, I have investigated the expression and function of TRP channels in diabetes because TRP channels have been shown to be involved in peripheral neuropathy as well as vascular complications in diabetes. ROS production plays a critical role in the progress of diabetes. I propose that lower levels of ROS up-regulate the expression TRP channels in the early stages of diabetes, leading to hyperalgesia, and higher levels of ROS or chronic exposure to ROS down-regulate TRP channels in the late stages of diabetes, resulting in hypoalgesia. I have found that the expression of TRPV1 and phospho p38 (p-p38) MAPK was increased in DRG of streptozotocin (STZ)-injected diabetic and non-diabetic hyperalgesic mice. An increase in TRPV1 and p-p38 MAPK levels was induced by STZ or H2O2 treatment in stably TRPV1 expressing HEK cells, suggesting the involvement of STZ-ROS-p38MAPK pathway. TRPV4 has been reported to be involved in vasodilatation by shear stress in blood vessels. Here, I have demonstrated that TRPV4 is expressed in lymphatic endothelial cells (LECs). Treatment with low concentration of H2O2 enhanced the expression of TRPV4 at mRNA and protein levels in LECs, suggesting that mild levels of ROS up-regulate TRPV4 expression. In diabetes, beta cell dysfunction is responsible for decreased insulin release. TRPV4 is expressed in RINm5F (beta cell line), islets and pancreas. It has been shown that hypotonicity induced insulin release in beta cell lines, which was mediated by activation of stretch-activated channels, raising the possibility of the involvement of TRPV4, a mechanosensitive channel. Therefore, I have studied the functional role of TRPV4 in beta cells. Incubation with 4alpha-PDD enhanced insulin release in RINm5F cells, suggesting TRPV4 regulates insulin secretion from pancreatic beta cells. Since TRPV4 expression levels are decreased in diabetes, insulin secretion from beta cells may be impaired. In summary, TRPV1, a thermosensitive channel, and TRPV4, a mechanosensitive channel, contribute to thermal and mechanical hyperalgesia, respectively in the early stage of DPN through their up-regulation by ROS-p38 MAPK and insulin/IGF-1 pathways. Due to the mechanical sensitivity of TRPV4 channel, the up-regulation in the early stage and down-regulation in the late stage may be involved in the development of vascular complications and regulation of insulin release in diabetes.
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Starr, Annalouise Bertina. "Mechanisms involved in transient receptor potential vanilloid receptor 1 (TRPV 1) mediated vasoactive responses." Thesis, King's College London (University of London), 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444546.
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Agustus, Daniel Joseph. "Transient receptor potential signalling in normal human urothelial cell cultures." Thesis, University of York, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.489187.
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The urothelium is a highly compliant, transitional epithelium that enables the bladder to accommodate urine during filling by alteration of its surface area. The urothelium was traditionally thought of as a passive barrier to ions and solutes. More recent data suggested that the urothelium may have a sensory function arising from the urothelial stretch-triggered release of chemical mediators such as ATP, as demonstrated in rabbit and cat. intracellular caicium signalling known to induce vesicle fusion and ATP release from neuronal cells; a similar mechanism may be responsible for urothelial ATP release.
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Pabbidi, Reddy M. "Role of transient receptor potential channels in diabetic peripheral neuropathy /." Available to subscribers only, 2007. http://proquest.umi.com/pqdweb?did=1456284721&sid=5&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Ogawa, Nozomi. "Detection of cellular redox status by transient receptor potential channels." 京都大学 (Kyoto University), 2016. http://hdl.handle.net/2433/215577.
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Bomben, Valerie Christine. "Role of transient receptor potential canonical channels in glioma cell biology." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2010. https://www.mhsl.uab.edu/dt/2010p/bomben.pdf.
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Oehler, Beatrice. "TRPA1 ist funktionell in Melanomzellen exprimiert, hat jedoch keinen Einfluss auf die verminderte Proliferation der Zellen nach Stimulation mit Senföl oder Zimtaldehyd." Doctoral thesis, Universitätsbibliothek Leipzig, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-116482.
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Melanome zählen zu den zehn häufigsten Tumorentitäten weltweit. Bei frühzeitiger Diagnose ist eine Exzision im Gesunden kurativ. Sobald eine Resektion im Gesunden jedoch nicht mehr möglich ist, sinken die Heilungschancen drastisch. Maligne Melanome sprechen wenig auf konventionelle Tumortherapien wie Radiatio und zytostatische Chemotherapie an. Daher werden neue Therapieoptionen in der Melanomtherapie getestet. Neueste Ansätze beziehen sich auf die Modulation von Immunzellen mittels monoklonaler Antikörper sowie die Modifikation der Signaltransduktion über die Mitogen-aktivierte Protein Kinase Kinase (MAPKK = MEK), BRAF und c-KIT. Auch Ionenkanäle stellen eine vielversprechende, zukünftige Option in der Behandlung maligner Melanome dar. Ich konnte zeigen, dass neben der bereits beschriebenen funktionellen Expression des „transient receptor potential“ Kanals TRPM8 in Melanomzelllinien auch TRPA1 in verschiedenen Melanomzelllinien exprimiert und funktionell ist. Die Phytopharmaka Senföl (Allylisothiozyanat; AITC) und Zimtaldehyd zeigen in Melanom-Modellen antitumoröse Effekte. Zudem sind beide Substanzen potente Stimulatoren von TRPA1. In dieser Arbeit wurde untersucht, ob AITC und Zimtaldehyd TRPA1-vermittelt die Proliferation, Apoptose und Migration von Melanomzellen beeinflussen. Das Vorkommen von TRPA1 in verschiedenen Melanomzelllinien wurde auf molekularbiologischer Ebene, mit fluorometrischen Bestimmungen des TRPA1-vermittelten Ca2+-Einstroms sowie in elektrophysiologischen Messungen nachgewiesen. Anschließend wurde die funktionelle Relevanz von TRPA1 bezüglich tumorhemmender Eigenschaften geprüft. Durch die Anwendung von TRPA1-Blockern konnte die AITC- und Zimtaldehyd-induzierte Verminderung der Proliferation nicht aufgehoben werden. Auch bezüglich der Migration und Apoptose konnte keine Korrelation zu einer TRPA1-Modulation festgestellt werden. Daher scheinen die durch AITC und Zimtaldehyd induzierten Effekte höchstwahrscheinlich nicht durch TRPA1 vermittelt zu werden.
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Pimentel, Montero Fátima Elizabeth. "Modulation of transient receptor potential melastatin 8 by protein kinase C /." Available to subscribers only, 2005. http://proquest.umi.com/pqdweb?did=1075689361&sid=10&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Kato, Kenta. "Characterization of bioactive molecules using genetically engineered ion channels." 京都大学 (Kyoto University), 2010. http://hdl.handle.net/2433/120897.
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Katisart, Teeraporn. "Transient receptor potential function in bladder from control and streptozotocin treated rats." Thesis, University of Hertfordshire, 2011. http://hdl.handle.net/2299/6039.
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Diabetic cystopathy is a chronic and common complication of diabetes with a classical triad of symptoms; decreased bladder sensation, increased bladder capacity and impaired detrusor muscle contractility (Hunter and Moore, 2003). In animal models of diabetes such as streptozotocin-induced diabetes in the rat, abnormalities of bladder function have been reported (Longhurst and Belis, 1986). The prototypic TRPV channel, TRPV1, is activated by capsaicin, which has been shown to cause contraction of the rat bladder (Saitoh et al., 2007), and this is reduced in STZ-diabetic rat bladder (Pinna et al., 1994). Therefore we hypothesize that TRPV1 function will be reduced in the diabetic bladder. The aim of this study are the following: Firstly, to investigate the effect of the streptozotocin (STZ) model of diabetes on a range of TRP channel functions in the urinary bladder smooth muscle preparation using TRP channel agonists and antagonists and to study the neurotransmitters involved in the contractile or relaxant responses. Some studies were also performed on colon tissues. Secondly, to explore the involvement of cholesterol modudation in TRP channel signalling. Thirdly, to study the change in TRP channel response with time following the treatment with streptozotocin. The results showed that the contractile responses to the TRPV1 agonist capsaicin, TRPV4 agonist 4-α-PDD, and TRPA1 agonist allyl isothiocyanate were significantly reduced in diabetic bladder. The selective TRPV1 antagonist, SB-366791, inhibited the contractile responses to capsaicin confirming the involvement of TRPV1 channels. The effect of diabetes is unlikely to be at the level of contractile machinery since the contractile responses to muscarinic receptor agonist carbachol were not significantly reduced in diabetic tissues. It is reported for the first time that the combination of neurokinin 1 and 2 antagonists GR-205171 and SB-207164 inhibited the contractile responses to capsaicin suggesting that a neurokinin may be the neurotransmitter involved in the capsaicin responses. In addition, the reduction of the responses to capsaicin in STZ-induced diabetic tissues occurred not only in urinary bladder but also in colon. Cholesterol-PEG significantly lowered the maximal contractile responses to capsaicin of rat bladder strips. Methyl-β-cyclodextrin, α-cyclodextrin and β-cyclodextrin at the same concentrations enhanced the contractile responses to capsaicin in the control and diabetic rat bladder strips. These effects of cyclodextrin are specific to capsaicin activated contractions and not seen with TRPA1 activation, suggesting that the effects are not mediated downstream of channel activation. Since α-cyclodextrin does not sequester cholesterol, the enhanced responses to cyclodextrins may not be due to the cholesterol modulations. Instead, theses novel findings may possibly occur by changing the local membrane lipid environment of the TRPV1 channel. As early as 36 hours after induction of diabetes by STZ, the contractile responses to capsaicin were significantly reduced in comparison to those of the controls and this reduction persisted until the eight weeks time point. In contrast, responses to the TRPA1 agonist allyl isothiocyanate were not affected at early time points but were reduced one week after STZ treatment. This detailed time course analysis suggests that there are novel mechanisms of modulation of the TRPV1 channels in this STZ model. In conclusion, in the rat urinary bladder or colon preparations, diabetes mellitus using STZ animal model caused 1) the impairment of a number of TRP channel subfamily functions, TRPV1, TRPV4 and TRPA1 but not TRPM8. The combination of NK1 and NK2 antagonists significantly inhibited the responses to capsaicin. This may suggest the involvement of neurokinin in postsynaptic transmission in rat bladder following the activation of TRPV1 channel, 2) the impairment caused by STZ-induced diabetes occurred very early (within 36 hours after diabetes induction) in TRPV1 channel but not TRPA1 channel. There are specific early effects of STZ treatment on TRPV1 channel function at a time when other afferent nerve terminal channels (TRPA1) are functioning normally, suggesting that early onset of dysfunction in TRPV1 signalling may not merely be the consequence of nerve damage, 3) the mechanism of this impairment may not be the effect of neuropathy on neurotransmitter release or nerve damage. Improving the responsiveness of nerves of bladder in diabetic patients might be of therapeutic benefit. The present studies suggest that it is possible to enhance function using indirect modulators such as bradykinin which potentiated the TRPV1 channel function in diabetic rat bladders.
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Mergler, Stefan, Monika Valtink, Sumioka Takayoshi, Yuka Okada, Masayasu Miyajima, Shizuya Saika, and Peter S. Reinach. "Temperature-Sensitive Transient Receptor Potential Channels in Corneal Tissue Layers and Cells." Karger, 2014. https://tud.qucosa.de/id/qucosa%3A71636.
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We here provide a brief summary of the characteristics of transient receptor potential channels (TRPs) identified in corneal tissue layers and cells. In general, TRPs are nonselective cation channels which are Ca ²⁺ permeable. Most TRPs serve as thermosensitive molecular sensors (thermo-TRPs). Based on their functional importance, the possibilities are described for drug-targeting TRP activity in a clinical setting. TRPs are expressed in various tissues of the eye including both human corneal epithelial and endothelial layers as well as stromal fibroblasts and stromal nerve fibers. TRP vanilloid type 1 (TRPV1) heat receptor, also known as capsaicin receptor, along with TRP melastatin type 8 (TRPM8) cold receptor, which is also known as menthol receptor, are prototypes of the thermo-TRP family. The TRPV1 functional channel is the most investigated TRP channel in these tissues, owing to its contribution to maintaining tissue homeostasis as well as eliciting wound healing responses to injury. Other thermo-TRP family members identified in these tissues are TRPV2, 3 and 4. Finally, there is the TRP ankyrin type 1 (TRPA1) cold receptor. All of these thermo-TRPs can be activated within specific temperature ranges and transduce such inputs into chemical and electrical signals. Although several recent studies have begun to unravel complex roles for thermo-TRPs such as TRPV1 in corneal layers and resident cells, additional studies are needed to further elucidate their roles in health and disease.
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Ghavideldarestani, Maryam. "Role of transient receptor potential channels in mammalian oviduct and uterine epithelia." Thesis, University of Hull, 2011. http://hydra.hull.ac.uk/resources/hull:6068.
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Calcium is an important secondary messenger and plays a major role in cell function, including proliferation, cell growth, secretion and death .It also plays a critical role in uterine smooth muscle contraction and embryo implantation. This thesis is concerned with calcium homeostasis in epithelial tissue lining the oviduct and uterus which are key players in early reproductive events, being involved in gamete transport, sperm capacitation and providing the micro-environment for the gametes and early embryo. Calcium transport across epithelial cells is either via tight junctions or calcium channels, specifically, members of the transient receptor potential (TRP) channel superfamily and the Na+/Ca2+ exchanger. TRP channels are an important class of calcium channels with more than 28 identified members and their potential involvement in calcium transport in uterus and oviduct epithelia has yet to be determined. The aim of this study was to discover which TRPC isoforms are expressed in epithelial cells lining the female reproductive tract in the bovine and human. Gene expression of TRPC channels changes was measured throughout the oestrous cycle in bovine oviduct and uterine epithelial cells using Real-Time PCR, while immunohistochemistry, immunocytochemistry and western blotting were used to discover the localization of TRPC channels in oviduct/uterine epithelium and changes in protein expression of TRPC isoforms induced by sex hormones. . to The physiological role of TRPC isoforms in regulating intracellular calcium concentration in bovine oviduct epithelial cells was determined using a calcium assay approach and finally. the potential clinical relevance of a possible role of TRP channels in female reproduction was investigated.# OF 7 members of TRPC family, TRPC1, 2, 3, 4 and 6 were expressed in bovine oviduct and uterine epithelia. In human endometrium, TRPC1, 6 and 7 genes were detected. Expression levels of all TRPC isoforms present in both bovine oviduct and uterine epithelia changed throughout the oestrous cycle. 17β-estradiol, FSH and LH individually and in combination up-regulated gene expression of TRPC isoforms in bovine oviduct epithelial cells. However, progesterone inhibited the upregulatory effect of 17β-estradiol, FSH and LH on TRPCs gene expression. TRPC1 and TRPC6 which are the common TRPC isoforms in bovine oviduct/uterine epithelium and human endometrium were localized on the apical, basal and lateral membranes of the epithelial tissue in bovine oviduct/uterus and human endometrium. TRPC isoforms were physiologically active in bovine oviduct epithelial cells (BOEC). SKF96365 which is a general TRP channel blocker inhibited the calcium influx into BOEC. Furthermore, Hyperforin which is a TRPC6 channel activator increased the intracellular calcium concentration in BOEC. TRPC1, 6 and 7 expression in endometrium of patients being treated for infertility by IVF illustrated that gene expression of TRTPC1 and 6 were up regulated in the endometrium of the IVF patients compared to controls. However, gene expression of TRPC7 in IVF patients was downregulated compared to that of the endometrium of the control group. Gene expression of TRPC6 and 7 in endometrium of women with Poly Cystic Ovarian Syndrome (PCOS) who have higher level of LH and normal FSH level, alongside the absence of the post-ovulatory increase in progesterone secretion, were up -regulated compared to that of the control group. However, the expression level of TRPC1 in endometrium of PCOS patients was not significantly different compared to the control group. Gene expression of TRPC isoforms in the epithelia lining the female reproductive tract is possibly regulated by sex hormones via nuclear factor-kappa B (NF-КB) signalling pathway. However, further investigation is required to determine the mechanisms underlying the endocrine regulation of TRPC channels.
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Myers, Benjamin R. "Genetic and evolutionary approaches to transient receptor potential channel structure and function." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3339199.
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Waddell, Trinity Q. "Role of Transient Receptor Potential Channels in Epithelial Morphogenesis in Chick Embryo." BYU ScholarsArchive, 2019. https://scholarsarchive.byu.edu/etd/8112.
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Transient Receptor Potential channels (TRP) are a superfamily of cationic specific ionchannels that are regulated by various stimuli such as temperature, pH, mechanical stress, ligandsand ion concentration. The role of TRP channels in disease states such as autosomal dominantpolycystic kidney disease, cancer metastasis, and developmental defects lend credence to thebelief that they play an important part in epithelial morphogenesis events. The development ofsomites, neural tube closure and migration of neural crest cells to form things such as the faceand heart is a good developmental model for the aforementioned cellular processes. We haveshown that TRP channels can be found in the developing ectoderm, hindbrain, and heart and thatthe inhibition of TRP channels in a developing embryo results in phenotypes suggestingperturbation of cellular remodeling processes. This leads to the question of the specific role ofTRP channels in the epithelial mesenchymal transition and remodeling in developing chickembryos.
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Sengupta, Sukanya. "Understanding the mechanisms of retinal degeneration in Drosophila lacking transient receptor potential channels." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609679.
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Curry, Haley Nicole. "Characterization of a Conserved Transient Receptor Potential Channel Supporting Spermatogenesis in Planarian Flatworms." Wright State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=wright1589976835122505.
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Aubdool, Aisah Aniisah. "The role of the Transient Receptor Potential Ankyrin-1 in the peripheral vasculature." Thesis, King's College London (University of London), 2014. https://kclpure.kcl.ac.uk/portal/en/theses/the-role-of-the-transient-receptor-potential-ankyrin1-in-the-peripheral-vasculature(c632b315-f86c-47f8-be01-55e1904550e1).html.
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The phenomenon of cold-induced vasodilatation (CIVD) was discovered by Sir Thomas Lewis (1930) and has been extensively investigated as it is involved in protecting against local cold-induced injury. The mechanisms underlying this well-established protective response remain unclear. The non-selective cation channel, transient receptor potential ankyrin-1 (TRPA1) is expressed in a subset of sensory neurons and acts as a polymodal membrane channel for cold sensitivity, but this remains a controversial issue in the literature. Additionally, the role of TRPA1 as a vascular cold sensor is currently unknown. Previous studies in our group have shown that TRPA1 plays an important role in regulating peripheral blood vessel tone, with little information available on the downstream signalling mechanism. The aims of this PhD project were to investigate the effects of TRPA1 activation by an exogenous agonist cinnamaldehyde and local cold exposure on peripheral vascular responses in murine skin in vivo. Using a combination of pharmacological antagonists and genetically modified mice, topical application of cinnamaldehyde (10%) was shown to increase blood flow in a TRPA1-dependent manner in the mouse ear model. This response was further shown to be dependent on the release of the potent microvascular vasodilator calcitonin gene-related peptide (CGRP), highlighting the involvement of a neurogenic component. This study provides novel evidence demonstrating the relative contribution of neuronal nitric-oxide synthase (nNOS)-derived nitric oxide and reactive oxygen species, downstream of TRPA1 activation by cinnamaldehyde. These findings highlight the prominent role of TRPA1 in mediating peripheral vasodilatation. The project further progressed to the development and characterisation of a local cold model in the mouse hindpaw in vivo. Local cold exposure was shown to cause a rapid and transient vasoconstriction, followed by a prolonged vasodilatation phase to return blood flow to baseline, an essential physiological function for protecting against local cold-induced injury. The activation of TRPA1 in the peripheral vasculature was shown to drive this cold-induced vascular response at 10°C. This model enabled the determination of the relative role of sympathetic nerves, post-junctional α2-adrenergic receptors and reactive oxygen species in the local cold-induced vasoconstriction. This study provides novel evidence showing that local cold exposure causes an increase in intracellular superoxide production in a TRPA1-dependent manner, which activates the Rho-kinase-mediated pathways and induces cold-induced α2C-adrenergic vasoconstriction. The neuropeptide CGRP was subsequently shown to have a prominent role in the vasodilator phase. This study provide novel evidence of a major involvement of TRPA1 in mediating cold-induced vasoconstriction in vivo, with a new perspective of the underlying mechanisms mediating the protection against local-cold induced injury.
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Bernardini, Michela. "Transient receptor potential (TRP) channel role in prostate cancer invasion and angiogenesis regulation." Thesis, Lille 1, 2015. http://www.theses.fr/2015LIL10157/document.
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Le cancer de la prostate (CaP) représente la deuxième cause de mortalité par cancer dans les pays développés. L'invasion des tissus environnants et l'angiogenèse tumorale promeut la métastase de CaP vers des organes éloignés. L’expression de plusieurs canaux TRP (Transient Receptor Potential) est dérégulée dans les cellules cancéreuses et les cellules endothéliales (CE) dérivées de tumeurs. Ils ont donc été proposés comme marqueurs pour la progression du cancer ainsi que comme cibles potentielles pour une thérapie pharmaceutique. Afin d'étudier les canaux TRP dans la vascularisation du CaP, nous avons isolé et caractérisé trois lignées de CE derivées du CaP (PTEC). Nous avons testé sur les PTEC l'effet de deux molécules anti-angiogénique en combinaison avec des médicaments anti-androgèniques. Les résultats démontrent un comportement résistant des PTEC à des médicaments anti-angiogéniques par rapport à des CE normales. Nous avons criblé l'expression de tous les canaux TRP dans les CE saines et celles dérivées de trois types tumoraux (prostate, sein, rein). Nous avons identifié cinq candidats ‘spécifiques’ du CaP dérégulés seulement dans les PTEC qui ont été caractérisés au niveau fonctionnel et leur rôle potentiel en tant que modulateurs de l'angiogenèse in vitro a été testé. En outre, nous avons étudié le rôle inhibiteur de TRPM8 dans la migration des cellules cancéreuses prostatiques CaP et nous avons également détecté TRPM8 dans les CE dans lesquelles nous avons observé aussi un rôle anti migratoire de TRPM8. Pris dans leur ensemble, nos résultats mettent en lumière de nouveaux acteurs moléculaires pour cibler sélectivement la progression du CaP et son angiogenèseProstate cancer (PCa) is the second most lethal male tumor in developed countries. Metastasis to distant organs is mainly mediated by tissue invasion and angiogenesis, which are indeed two of the main cancer hallmarks. Several Transient Receptor Potential (TRP) proteins are deregulated in cancer cells and angiogenesis and have been suggested as valuable markers in predicting cancer progress and as potential targets for pharmaceutical therapy. In order to screen and study TRP channels in PCa vasculature, we isolated and characterized three lines of human endothelial cells (ECs) from PCa patients (PTEC). We tested the effect of two anti-angiogenic in combination with anti-androgen drugs. The results clearly demonstrate a resistant behavior of endothelial cells isolated from prostate cancer to specific anti-angiogenic drugs compared to normal endothelial cells. We fully profiled the expression of TRP channels in tumor (prostate, breast and renal) and healthy ECs, with particular interest for prostate tumor EC. We identified five ‘prostate specific’ candidates deregulated in PTEC compared to endothelial derived from healthy prostate. ‘Prostate specific’ TRP candidates were functionally characterized and their potential role as in vitro angiogenesis modulators investigated. Our laboratory has already extensively studied the role of TRPM8 in PCa progression and migration. For this reason, we further investigated the molecular mechanism underling this effect in PCa cells as well as in ECs. Taken together, our results bring to light TRP channels as novel molecular players to selectively target prostate tumor progression and angiogenesis
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Baxter, Matthew. "The role of Transient Receptor Potential (TRP) channels in the pathogenesis of COPD." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/29840.
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COPD is currently the 4th most prevalent cause of death worldwide. Despite the global impact, there are no currently available treatments which impede disease progression. This lack of effective therapies is largely due to an inadequate understanding of the mechanisms which drive disease progression. Cigarette smoke (CS), the most important risk factor for COPD, is thought to initiate an inflammatory response in the lungs which becomes self-propagating and dysregulated. Chronically, this inflammatory response drives structural and functional changes. The mechanisms by which CS elicits this inflammatory response, however, remain unclear. Certain CS constituents are known to activate Transient Receptor Potential (TRP) ion channels. A number of TRP channels are actively expressed in the lung tissue or inflammatory cells, and a further few are also implicated in the generation of inflammation. Owing to these features, it was hypothesised that TRP channels A1, C6, M2, M8, V1 and V4 have a role in CS-induced airway inflammation and, consequently, the pathogenesis of COPD. To test this hypothesis, three murine models of induced airway inflammation were characterised: acute CS, sub-chronic CS and endotoxin (LPS). Lung-tissue TRP channel expression levels were measured in these models alongside human lung-parenchyma samples from non-smokers, smokers and emphysema patients. Mice deficient for specific TRP channels were profiled in the CS-model and the LPS-model to establish the role of TRP channels in the initiation of inflammation in disease and non-disease settings. TRPV1-/-, TRPV4-/- and TRPM8-/- mice exhibited significantly reduced levels of airway inflammation compared to wild-types after acute CS, but normal responses to the innate (LPS) challenge. This data suggests that modulation of TRP channels could represent a novel anti-inflammatory approach for combating smoke induced diseases like COPD without impacting on the normal, essential innate defence mechanisms.
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Bodkin, Jennifer. "Investigating the role of Transient Receptor Potential Ankyrin One (TRPA1) in cardiovascular regulation." Thesis, King's College London (University of London), 2012. https://kclpure.kcl.ac.uk/portal/en/theses/investigating-the-role-of-transient-receptor-potential-ankyrin-one-trpa1-in-cardiovascular-regulation(86e661c9-d299-45cd-b3d3-b23fe18f9181).html.
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TRPA1 is a member of the TRP superfamily; localised to neural and non-neuronal sites. TRPA1 is activated endogenously by products of oxidative stress, where its expression on sensory neurones leads to the release of vasoactive neuropeptides. Exogenous agonists of TRPAl, mustard oil and cinnamaldehyde, have been shown to cause concentration-dependent vasorelaxation of blood vessels via a variety of mechanisms. My PhD used TRPA1 WT and KO mice to investigate the potential for TRPA1 to alter peripheral artery tone and the implications of this on systemic blood pressure. I also studied the development of angiotensin II induced hypertension and associated pathologies. Wire myography using murine TRPA1 WT and KO mesenteric arteries showed cinnamaldehyde to cause concentration-dependent vasorelaxation comprising a TRPA1 dependent component, which was endothelial independent and mediated by CGRP and hyperpolarisaton. Basal blood pressure monitoring by both tail cuff plethysmography and telemetry showed no overall effect of TRPA1 deletion on basal hemodynamics. However, TRPAl KO mice displayed a previously unreported hyperactivity phenotype, measured by both telemetry and voluntary wheel running. 14 day infusion of angiotensin II by osmotic minipump induced similar hypertension in both TRPA1 WT and KO mice. Hypertrophy of the heart was seen in both genotypes, but of significantly increased magnitude in TRPA1 KO mice. Further analysis of associated inflammatory biomarkers by RT qPCR and MSD multiplex ELISA showed upregulation of pro-oxidative genes in hypertensive mice of both genotype. This was significantly greater in hypertensive TRPA1 KO mice than in hypertensive TRPA1 WT mice. These findings may partially explain the increase in hypertrophy in these mice. Angiotensin II infused mice of both genotypes showed increases in chemokine and cytokine expression. Striking, increases in IL6 and MCP-1 seen in hypertensive WT mice were significantly blunted in hypertensive KO mice, suggesting that TRPAl may differentially modulate inflammatory responses.
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Walker, Rebecca L. "Functional and molecular characterization of TRP channels in smooth muscle /." abstract and full text PDF (UNR users only), 2002. http://0-gateway.proquest.com.innopac.library.unr.edu/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3068507.
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Che, Hui, and 車慧. "Functional transient receptor potential channels in human preadipocytes and cardiac c-kit⁺ progenitor cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196436.
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Transient receptor potential (TRP) channels play important roles in cellular physiology and biology. The present PhD project investigated the functional expression of TRPV and TRPM channels in human preadipocytes and cardiac c-kit+ progenitor cells and their roles in regulating cell proliferation, adipogenic differentiation or migration. In addition, the role of store-operated Ca2+ entry (SOCE) channels in regulating cell proliferation and migration was also studied in human cardiac c-kit+ progenitor cells using multiple approaches including whole-cell patch voltage-clamp, confocal microscope, molecular biology, etc.
We found that TRPV2, TRPV4 and TRPM7 channels were abundantly expressed in human preadipocytes. Activation of TRPV2 channels by probenecid caused a long-lasting intracellular Ca2+ transient, while activation of TRPV4 channels by 4-PDD induced Ca2+ oscillations. TRPM7 current was recorded with a Mg2+-free pipette solution, and inhibited by 2-aminoethyl diphenyl borate (2-APB). Silence of TRPV2 or TRPM7, but not TRPV4, with the specific shRNA, reduced cell proliferation via inhibiting cyclin D1, cyclin E, and p-ERK1/2. Individually silencing these three channels decreased adipogenic differentiation by reducing p-Akt kinase. The results indicate that TRPV2, TRPV4 and TRPM7 are involved in adipogenesis, while TRPV2 and TRPM7, but not TRPV4, regulate cell proliferation in human preadipocytes.
In second part of the thesis, abundant expression of TRPV2, TRPV4, and TRPM7 channels was demonstrated in human cardiac c-kit+ progenitor cells. Similar to human preadipocytes, probenecid and 4-PDD activated Ca2+ signaling, and TRPM7 current recorded with a Mg2+-free pipette solution was inhibited by 2-APB. Silencing TRPV2 or TRPM7, but not TRPV4, inhibited cell proliferation by arresting cells at G0/G1 phase with a reduced cyclin D, cyclin E, and p-ERK1/2. Cell migration was decreased with silence of TRPV2, TRV4 or TRPM7 via inhibiting p-Akt kinase. The results show that TRPV2, TRPV4 and TRPM7 mediate cell migration, while TRPV2 and TRPM7, but not TRPV4 channels, participate in regulating cell proliferation.
In third part of the thesis, we demonstrated that SOCE channels were composed of TRPC1, STIM1 and Orai1 by protein-protein interaction. Silence of TRPC1, STIM1, or Orai1 with specific siRNA reduced Ca2+ influx through SOCE channels, decreased cell proliferation by inhibiting cyclin D1 and cyclin E, and slowed down cell migration via reducing p-Akt kinase. These results suggest that TRPC1, STIM1 and Orai1 are the major components of SOCE channels in human cardiac c-kit+ cells. SOCE channels play an essential role in regulating cell proliferation and migration.
Collectively, this PhD project has demonstrated for the first time that 1) TRPV2, TRPV4, and TRPM7 are abundantly expressed in human preadipocytes and cardiac c-kit+ progenitor cells. 2) These TRP channels regulate adipogenic differentiation in preadipocytes and migration in cardiac c-kit+ progenitor cells. 3) TRPV2 and TRPM7, but not TRPV4, are involved in cell proliferation of human preadipocytes and cardiac c-kit+ progenitor cells. 4) TRPC1, STIM1 and Orai1 are interacted to form SOCE channels and regulate cell proliferation and migration in human cardiac c-kit+ cells. 5) All the above physiological roles of TRPV2, TRPV4, TRPM7, and SOCE channels are mediated by cyclin D1, cyclin E, p-ERK1/2, and/or p-Akt.published_or_final_version
Medicine
Doctoral
Doctor of Philosophy
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Venkataraman, Rajarajeshwari. "ROLE OF TRANSIENT RECEPTOR POTENTIAL CANONICAL-6 (TRPC6) CHANNEL IN METASTASIS OF GLIOBLASTOMA MULTIFORME." Master's thesis, University of Central Florida, 2008. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4353.
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Glioblastoma multiforme (GBM) is one of the extremely fatal brain tumors. The main reason that makes it so lethal is its capability to invade and spread to other parts of CNS producing secondary tumors. Among other factors hypoxia, reduced oxygen availability, is linked to higher metastatic potential of cancers. Hypoxia causes numerous changes in genome and proteome of the cell. These changes help a normal cell to adapt to nutritional deficiency, but the same changes can increase the malignancy and metastasis in tumor cells. Extensive research by a number of curious scientists reveal that various pathways involving numerous proteins cross-talk and interact with each other and execute a response to hypoxia. We are trying to establish the link between two such pathways HIF1-alpha pathway and Notch pathway. Both, HIF1-alpha, which is a transcription factor that becomes active in hypoxic conditions and Notch, which is an evolutionarily conserved cell-fate determinant, are implicated in hypoxia-induced metastasis of cancer. In this given project, we confirm the cross talk between Notch and HIF1-alpha pathway and further continue our study to show that TrpC6 is the downstream mediator of this pathway, leading to metastasis of GBM. Expression analysis of hypoxia-induced U373 cells (Grade 3 glioblastoma cells), using Real-time PCR, western blot and immunocytochemistry, revealed elevated levels of Notch, Hif1 and TrpC6 indicating that these proteins might be important for the cellular response to hypoxia. Blocking Notch and/or HIF1-alpha, either by DAPT or HIF1-inhibitor, confirmed the communication between these two pathways. Role of TrpC6 in metastasis was demonstrated by knocking down this gene using siRNA against TrpC6. Inhibition of TrpC6 markedly decreased cell proliferation, migration, angiogenesis and tumorigenesis in these hypoxia-induced Glioblastoma cells. In summary, all these results reveal that TrpC6 is indeed an important member of the Notch-mediated metastasis of Glioblastoma under hypoxic conditions. This role of TrpC6 can therefore be utilized for pharmacological intervention to prevent hypoxia-induced metastasis in GBM.M.S.
Department of Molecular Biology and Microbiology
Burnett College of Biomedical Sciences
Molecular and Microbiology MS
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Ni, Dan. "THERMAL SENSITIVITY OF VAGAL PULMONARY SENSORY NEURONS: ROLE OF TRANSIENT RECEPTOR POTENTIAL VANILLOID CHANNELS." Lexington, Ky. : [University of Kentucky Libraries], 2008. http://hdl.handle.net/10225/944.
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Thesis (Ph. D.)--University of Kentucky, 2008.Title from document title page (viewed on December 10, 2008). Document formatted into pages; contains: x, 73 p. : ill. (some col.) Includes abstract and vita. Includes bibliographical references (p. 62-71).
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Ralphs, Katherine L. "Characterisation of the localisation and function of the mammalian transient receptor potential channel seven." Thesis, University of Bath, 2005. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415762.
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Dahan, Diana. "Etude des mécanismes cellulaires de l'hypertension artérielle pulmonaire : rôle des canaux TRPV dans l'hyperréactivité et le remodelage des artères pulmonaires de rat." Thesis, Bordeaux 2, 2011. http://www.theses.fr/2011BOR21843/document.
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L’hypertension pulmonaire (HTP) est la principale pathologie de la circulation pulmonaire et a un très mauvais pronostic. Elle se caractérise par une hyperréactivité et un remodelage des petites artères pulmonaires (AP) entraînant une augmentation progressive des résistances vasculaires pulmonaires, qui, ultimement, aboutit à une insuffisance cardiaque droite et au décès du patient. Il est admit que le calcium joue un rôle très important aussi bien dans les mécanismes de remodelage que dans l’hyperréactivité des AP observés dans l’HTP. Dans le présent travail, nous avons étudié l’expression et le rôle d’une famille particulière de canaux calciques, les TRPV, dans les AP de rats contrôles (normoxiques) et souffrant d’hypertension pulmonaire (rats hypoxiques chroniques et traités à la monocrotaline). Nous montrons que (1) les canaux TRPV1, V2 et V4 sont exprimés dans les AP et que cette expression est augmentée au cours de l’HTP ; (2) la stimulation de ces canaux par des agonistes spécifiques induit une augmentation de la concentration calcique intracellulaire dans les cellules musculaires lisses (CML) ; (3) le récepteur à la ryanodine de type 2 (RRy 2) du réticulum sarcoplasmique est impliqué dans la voie de signalisation dépendante de TRPV4 et que son expression est également augmentée au cours de l’HTP ; (4) les canaux TRPV1 et TRPV4 sont impliqués dans la migration des CML, processus fondamental du remodelage ; (5) les contractions induites par l’activation de TRPV2 et TRPV4 dans les AP de rats hypertendus sont significativement diminuées par la streptomycine, un inhibiteur des canaux SAC (stretch activated channels). Ce travail démontre donc l’implication des canaux TRPV à la fois dans l’hyperréactivté et le remodelage des AP. De nouveaux traitements ciblant les canaux TRPV pourraient constituer une approche thérapeutique innovante de l’hypertension pulmonairePulmonary hypertension (PH)) is the primary pathology of the pulmonary circulation and has a very bad prognostic. This disease is characterized by a hyperreactivity and remodelling of small pulmonary arteries (PA) leading to a progressive increase in pulmonary vascular resistance which ultimately leads to right heart failure and death of the patient. It is admitted that calcium plays an important role both in the mechanisms of remodelling and in the hyperresponsiveness of PA observed in PH. In the present work, we studied the expression and the role of a particular family of calcium channels, TRPV channels, in PA from control rats (normoxic) and pulmonary hypertensive rats (chronically hypoxic and monocrotaline-treated rats). We show that (1) TRPV1, V2 and V4 channels are expressed in the PA and that their expression are increased in PH; (2) stimulation of these channels by specific agonists induces an increase in the intracellular calcium concentration in smooth muscle cells (SMC), (3) the ryanodine receptor type 2 (RRy2) of the sarcoplasmic reticulum is involved in the TRPV4-dependent signaling pathway and its expression is also increased in PH, (4) TRPV1 and TRPV4 channels are involved in the migration of SMC, the fundamental process of remodelling, (5) contractions induced by activation of TRPV2 and TRPV4 in the PA from hypertensive rats are significantly decreased by streptomycine, an inhibitor of stretch activated channels (SAC). This work thus demonstrates the involvement of TRPV channels in both the hyperreactivity and remodelling of PA. New treatments targeting TRPV channels could be an innovative therapeutic approach for pulmonary hypertension
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Hovsepian, Anahit [Verfasser]. "Regulation von Transient Receptor Potential Canonical Typ 3-Kanälen (TRPC3) bei chronischer Niereninsuffizienz / Anahit Hovsepian." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2010. http://d-nb.info/1023964864/34.
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Liu, Ying [Verfasser]. "Regulation of transient receptor potential canonical channels TRPC3 and TRPC6 in kidney diseases / Ying Liu." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2013. http://d-nb.info/103109749X/34.
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Shaifta, Yasin Mohammad. "Transient receptor potential channels (TRPC) in human cells : characterisation using over expression and knock-down." Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.429098.
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Cai, Shiwei. "The transient receptor potential channel 1 (TRPC1) mediates calcium-regulated differentiation in oral gingival keratinocytes /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/6390.
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Sulak, Michael A. "Modulation of Transient Receptor Potential Cation Channel, Subfamily A, Member 1 (TRPA1) Activity by Cdk5." Kent State University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=kent1322494947.
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Engelke, Michael. "Untersuchung des Einflusses von "Transient-Receptor Potential"-Proteinen auf den Ca2-1hn+-Einstrom in B-Zellen." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=96777019X.
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Günther, Franziska [Verfasser], David [Akademischer Betreuer] Andersson, and Helmut Johann [Gutachter] Brandstätter. "Transient Receptor Potential Ankyrin 1 in Diabetes / Franziska Günther ; Gutachter: Helmut Johann Brandstätter ; Betreuer: David Andersson." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2019. http://d-nb.info/1191994015/34.
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Grimm, Christian [Verfasser]. "Endolysosomal Cation Channels of the Transient Receptor Potential Superfamily : Physiology, Pharmacology, and Mouse Models / Christian Grimm." München : GRIN Verlag GmbH, 2014. http://d-nb.info/1067618155/34.
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Clarke, Rebecca. "An in vitro model for the study of transient receptor potential channels on human sensory neurons." Thesis, Queen's University Belfast, 2015. https://pure.qub.ac.uk/portal/en/theses/an-in-vitro-model-for-the-study-of-transient-receptor-potential-channels-on-human-sensory-neurons(0030aff3-6cb4-43bb-9a40-3e5cbc24c4bc).html.
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Sensory neurons are responsible for detecting noxious chemical, mechanical and thermal stimuli and relaying the information to the central nervous system. They also contribute to local neurogenic inflammation via the release of neuropeptides. Sensory neurons express a variety of ion channels, including the transient receptor potential (TRP) channels. TRP channels are one of the main families of ion channels responsible for nociception and are desirable targets for analgesic and anti-inflammatory therapies. TRP channel studies on human sensory neurons has been hampered by the fact that peripheral neurons lack theis cell bodies, which are housed in neuronal ganglia and are inaccessible via peripheral tissue biopsy. To overcome this limitation we have differentiated human dental pulp stem cells towards a neuronal phenotype, termed peripheral neuronal equivalebts (PNEs), which have their cell bodies present. Microfluorimetric and electrophysiological techniques have demonstrated the functional expression of TRP channels on PNEs, specifically TRPA 1 and TRPV1. Therefore PNEs represent a novel source of functional human sensory neurons suitable for in vitro TRP channel studies. In vivo, neuronal TRP channels become hypersensitised in inflammatory and infectious environments however the exact mechanism through which this occurs is unknown. PNEs pre-treated with pro-inflammatory cytokines generated larger responses to TRP channel agonists when compared to untreated PNEs however no alterations in TRP channel gene expression were observed. PNEs infected with human rhinovirus also show no change in TRP channel gene expression suggesting that TRP channel sensitisation, rather than upregulation, contributes to nerve hypersensitivity.
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Liu, Pin. "Fat Taste Transduction in Mouse Taste Cells: The Role of Transient Receptor Potential Channel Type M5." DigitalCommons@USU, 2010. https://digitalcommons.usu.edu/etd/824.
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A number of studies have demonstrated the ability of free fatty acids to activate taste cells and elicit behavioral responses consistent with there being a taste of fat. Here I show for the first time that long chain unsaturated free fatty acid, linoleic acid, depolarizes taste cells and elicits a robust intracellular calcium rise via the activation of transient receptor potential channel type M5. The linoleic acid-induced responses depend on G protein-phospholipase C pathway indicative of the involvement of G protein-coupled receptors in the transduction of fatty acids. Mice lacking transient receptor potential channel type M5 exhibit no preference for and show reduced sensitivity to linoleic acid. Together, these studies show that transient receptor potential channel type M5 plays an essential role in fatty acid transduction and suggest that fat may reflect a bona fide sixth primary taste. Studies to identify the types of taste cells that respond to fatty acids show that both type II and type III taste cells express fatty acid-activated receptors. Fatty acids elicit robust intracellular calcium rise primarily in type II taste cells and a subset of type III taste cells. However, a significant subset of type II taste cells respond to high potassium chloride, which has been broadly used as the indicator for type III taste cells as well, suggesting the expression of voltage-gated calcium channels in these cells. This finding conflicts with previous studies that type II taste cells lack voltage-gated calcium channels. To explore if voltage-gated calcium channels are expressed in subsets of type II taste cells, transgenic mice with type II or III taste cells marked by green fluorescent proteins are used. Results show that a subset of type II taste cells exhibit voltage-gated calcium currents, verifying the expression of voltage-gated calcium channels in these cells. These results question the utility of being able to use high potassium chloride solution to identify unequivocally type III taste cells within the taste buds. A model for the transduction of fatty acids in taste cells consistent with these findings and our previous data is presented.
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Chretien, Chloé. "Un nouvel acteur dans la détection hypothalamique du glucose : les canaux Transient Receptor Potential Canonical (TRPC)." Thesis, Dijon, 2015. http://www.theses.fr/2015DIJOS027/document.
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L’hyperglycémie est détectée et intégrée au niveau de l’hypothalamus médio-basal (MBH) qui inhibe la prise alimentaire et déclenche la sécrétion d’insuline. Le MBH renferme des neurones spécialisés gluco-sensibles (GS) qui détectent directement ou indirectement des variations de la concentration extracellulaire en glucose. Dans une première étude, nous suggérons que la détection indirecte du glucose par les neurones GS hypothalamiques repose sur la libération d’endozépines par les astrocytes, un gliotransmetteur connu pour inhiber la prise alimentaire en réponse à l’hyperglycémie. Nous travaux montrent que les endozépines activent spécifiquement les neurones à pro-opiomélanocortine (POMC) du MBH pour générer leur effet anorexigène. Dans une seconde étude, nous montrons que la détection directe de l’hyperglycémie implique les neurones hypothalamiques dits « high gluco-excited » (HGE). Grâce à des approches pharmacologiques et génétiques, nous mettons en évidence que les canaux redox sensibles Transient Receptor Potential Canonical 3 et 4 (TRPC3/4) sont fondamentaux pour la détection du glucose par les neurones HGE in vitro, la stimulation de la sécrétion d’insuline et la diminution de la prise alimentaire en réponse à l’hyperglycémie cérébrale in vivo. De plus, nos travaux démontrent que les canaux TRPC3 du MBH jouent un rôle clef dans le contrôle de l’homéostasie énergétique. Les travaux de cette thèse permettent de mettre en évidence deux nouveaux mécanismes de détection hypothalamique de l’hyperglycémie : l’un reposant sur l’implication des canaux TRPC3/4 dans les neurones HGE et l’autre proposant les endozépines astrocytaires comme relai du signal « glucose » aux neurones POMCHyperglycemia is detected and integrated by the mediobasal hypothalamus (MBH) which, in turn, inhibits food intake and triggers insulin secretion. The MBH houses specialized glucose-sensitive (GS) neurons, which directly or indirectly modulate their electrical activity in response to changes in glucose level. In a first study, we hypothesized that indirect detection of glucose by MBH GS neurons involves the secretion of endozepine by astrocytes, a gliotransmitter known to inhibit food intake in response to hyperglycemia. The present work shows that endozepines selectively activate anorexigenic MBH pro-opiomelanotortine (POMC) neurons. In the second study, we show that the direct detection of increased glucose level involves hypothalamic glucose-excited (HGE) neurons. Using pharmacological and genetic approaches, we demonstrate that the redox-sensitive Transient Receptor Potential Canonical 3 et 4 (TRPC3/4) channels are involved in MBH HGE response to glucose in vitro and increased insulin secretion and decreased food intake in response to cerebral hyperglycemia in vivo. We also obtained evidences that MBH TRPC3 channel is a critical new player for energy homeostasis. This thesis work identifies two new mechanisms involved in hypothalamic detection of hyperglycemia: the first based on the involvement of TRPC3/4 channels in HGE neurons and the second highlighting the astroglial endozepines as a relay of the “glucose” signal to POMC neurons
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Bonet, Ivan José Magayewski 1986. "O papel do receptor TRPA1 no desenvolvimento e manutenção da hiperalgesia induzida pela carragenina." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314055.
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Orientador: Cláudia Herrera TambeliDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-22T19:36:40Z (GMT). No. of bitstreams: 1 Bonet_IvanJoseMagayewski_M.pdf: 8243433 bytes, checksum: a5cdaab90bdcc5bbba66a0e5e4a1293f (MD5) Previous issue date: 2013
Resumo: O Receptor Potencial Transiente Ankiryn 1 (TRPA1) é um canal não seletivo a cátions importante na fixação do limiar nociceptivos e pertencente à superfamília de canais TRP. É expresso em fibra C-nociceptiva e células não neuronais envolvidas na liberação de mediadores pró-inflamatórios. No presente estudo, investigamos se o TRPA1 contribui para a hiperalgesia induzida pela carragenina em ratos, e se essa contribuição é mediada por mecanismos de inflamação, tais como liberação de citocinas pró-inflamatórias e migração de neutrófilos e/ou sensibilização direta do neurônio aferente primário. Avaliamos a sensibilização do nociceptor induzida pela carragenina utilizando estímulos mecânico (analgesímetro mecânico) e químico (capsaicina), com ou sem bloqueio farmacológico local do receptor TRPA1 pelo seu antagonista seletivo HC 030031. A carragenina induziu hiperalgesia com pico na terceira hora, persistindo até vigésima quarta hora. O bloqueio farmacológico do receptor TRPA1 por co-administração de HC 030031 diminuiu significativamente a hiperalgesia induzida pela carragenina na terceira hora e a pós-administração de HC 030031 (2hrs 55min) reduziu na terceira e na sexta hora. O silenciamento do gene do TRPA1, induzido por um pré-tratamento intratecal com Oligonucleotídeo antisense, preveniu a hiperalgesia induzida pela carragenina após 24 horas além de reduzir significativamente a expressão de TRPA1 em células dos gânglios da raiz dorsal (GRD) (L5-6). O tratamento com carragenina, por sua vez, não alterou a expressão do receptor TRPA1 no GRD, e tampouco afetou os níveis de citocinas e a migração de neutrófilos no tecido periférico (patas). Concluímos que TRPA1 tem papel importante no desenvolvimento e manutenção da hiperalgesia inflamatória induzida pela carragenina por contribuir diretamente na excitabilidade do nociceptor. Baseado nesses achados, sugerimos que o bloqueio de TRPA1 é uma estratégia promissora no desenvolvimento de futuras drogas para o controle e tratamento da dor
Abstract: The Transient Receptor Potential Ankiryn 1 (TRPA1) is a nonselective cation channel, important in setting nociceptive threshold belonging to the superfamily of TRP channels. It is expressed in nociceptive C-fibers and in non-neuronal cells involved in pro-inflammatory mediators release. In this study, we asked whether TRPA1 contributes to carrageenan-induced hyperalgesia in rats, and whether this contribution is mediated by mechanisms in inflammation, such as cytokine release and neutrophil migration and/or by a direct sensitization of the primary afferent nociceptors. We measured the carrageenan-induced nociceptive sensitization using a mechanical (mechanical analgesymeter) and a chemical (capsaicin) stimulus, with or without pharmacological blockade of TRPA1 by its selective antagonist HC 030031. Carrageenan-induced Hiperalgesia has peaked at the third hour and persisted until the twenty-fourth hour. Pharmacological blockade of TRPA1 receptor by co-administration of HC 030031 significantly lowered carrageenan-induced hiperalgesia at the third hour and post-administration (2hrs 55min) decreased at both third and sixth hours. The neuronal TRPA1 gene silencing induced by intrathecal pre-treatment with antisense oligodoexynucleotide completely prevented carrageenan-induced hyperalgesia over 24 hours and significantly reduced TRPA1 expression in the dorsal root ganglia cells (DRG ) (L5-6). However, carrageenan treatment, did not affect the TRPA1 expression on DRG, neither affected the cytokines levels and neutrophil migration in peripheral tissue (paws). We conclude that TRPA1 plays an important role in the development and maintenance of carrageenan-induced inflammatory hyperalgesia by directly contributing to nociceptor excitability. Based on these findings, we suggest that TRPA1 blockade is a promising strategy for the development of future drugs to pain treatment and control
Mestrado
Fisiologia
Mestre em Biologia Funcional e Molecular
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Takahashi, Nobuaki. "TRP channels as sensors of cellular redox status." 京都大学 (Kyoto University), 2010. http://hdl.handle.net/2433/131892.
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Yin, Jun [Verfasser]. "Functional relevance and regulation of Transient Receptor Potential Vanilloid 4 channel in hydrostatic lung edema / Jun Yin." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2009. http://d-nb.info/1023666162/34.
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Shang, Ye. "Mechanisms Regulating Transient Receptor Potential Cation Channel A1 (TRPA1) and Their Roles in Nociception and Nociceptive Sensitization." eScholarship@UMMS, 2020. https://escholarship.umassmed.edu/gsbs_diss/1092.
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Nociception is the sensory nervous system that detects harmful stimuli including excessive heat, cold, toxic chemicals, and noxious mechanical stimulations. Transient receptor potential (TRP) channels are a group of evolutionarily conserved ion channels consisting of 4 subunits, each with 6 transmembrane spans, and detect a variety of external and internal nociceptive stimuli. Due to their critical roles in nociception, it is essential to understand the mechanisms that regulate TRP channels and subsequent nociception. Here, I investigated two distinct types of regulation of Drosophila transient receptor potential cation channel A1 (TrpA1): regulation via the expression of different TrpA1 isoforms, and via its binding with associated proteins. I found that one of the TrpA1 isoforms, TrpA1(E), inhibits the thermal responses of other TrpA1 isoforms in vitro. I also identified potential TrpA1 binding partners through Co- immunoprecipitation (Co-IP) and mass spectrometry analysis. These binding partners need further validation and characterization through biochemical, cellular, and behavioral assays to illustrate their roles in nociception, and may serve as potential drug targets for chronic pain.
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Unger, Nicholas T. "Blockade of the Transient Receptor Potential Vanilloid (TRPV) by Ruthenium Red Does Not Suppress Hypothalamic Neuronal Thermosensitivity." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1331060091.
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Solanki, Sumeet A. ""Novel Role of the Transient Receptor Potential Canonical 3 (TRPC3) channel in Macrophage Apoptosis: Implications in Atherosclerosis”." University of Toledo Health Science Campus / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=mco1492707181753622.
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