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Hering, Nils [Verfasser]. "Elektrophysiologische Charakterisierung der Ionenkanäle TRPV1, TRPV3 und TRPV4 exprimiert in Xenopus Oozyten. / Nils Hering". Kiel : Universitätsbibliothek Kiel, 2016. http://d-nb.info/1096220881/34.
Pełny tekst źródłaHasan, S. M. Raquibul. "Modulation of the TRPA1 and TRPV1 ion channels". Thesis, University of Cambridge, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708079.
Pełny tekst źródłaHellwig, Nicole. "Protonenleitfähigkeit von TRPV1 und Multimerisierung von TRPV-Kanaluntereinheiten". [S.l.] : [s.n.], 2005. http://www.diss.fu-berlin.de/2005/177/index.html.
Pełny tekst źródłaSinha, Sayantani. "Role of TRPA1 and TRPV1 in Propofol Induced Vasodilation". Thesis, Kent State University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3618926.
Pełny tekst źródłaAims: Propofol, clinically named as Diprivan is an intravenous anesthetic known to cause hypotension in patients presenting for surgery. We have investigated the vasodilatory signaling cascade by which propofol causes hypotension using both in vivo and in vitro experimental approaches.
Methods and Results: Using high-fidelity microtip transducer catheter, mean arterial blood pressure (MAP) was measured in control, transient receptor potential ankyrin subtype 1 knock-out (TRPA1-/-), transient receptor potential vanilloid 1 knock-out (TRPV1-/-) and TRPA1-TRPV1 double-knockout mice (TRPAV-/-) in the presence and absence of L-NAME (an endothelial nitric oxide synthase inhibitor) and penitrem A [a big-conductance calcium gated (BKCa) channel inhibitor]. To further support our in-vivo data, murine coronary microvessels were isolated and cannulated for vasoreactivity studies. Furthermore, NO production from endothelial cells isolated from mouse aorta was also measured and immunocytochemical (ICC) studies were performed to show the intracellular localization of TRPA1 and TRPV1. Our in-vivo data shows that the characteristic propofol-induced depressor response is dependent on TRPA1-NO-BKCa pathway. Interestingly, vasoreactivity studies in isolated murine left anterior ascending (LAD) arteries demonstrate that TRPA1 and TRPV1 communicate with each other and propofol-induced vasodilation is dependent on both TRPA1 and TRPV1. Moreover our data also suggest that NO production and BK channel activation are the downstream mediators in this pathway. Finally, we demonstrate that NO production is attenuated in primary endothelial cells isolated from TRPAV-/- mice. ICC data also shows the co-localization of these channels in mouse aortic endothelial cells.
Conclusions: This is the first study which has shown that propofol-induced vasodilation involves TRPA1 in-vivo and also there is an implication of cross-talk between TRPA1 and TRPV1 in the coronary bed. Furthermore by understanding the mechanisms by which this anesthetic causes hypotension and coronary dilation will help to mitigate the potential harmful side-effects of anesthesia in patients with little cardiovascular reserve. This will in turn ensure a better and faster post-operative recovery in patients, especially benefiting those suffering from diabetes and other cardiovascular disorders.
SINHA, SAYANTANI. "Role of TRPA1 and TRPV1 in Propofol Induced Vasodilation". Kent State University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=kent1384901930.
Pełny tekst źródłaSprague, Jared Michael. "TRPV1 Sensitization in Primary Sensory Neurons". Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11441.
Pełny tekst źródłaO'Leary, Caitriona. "The role of TRPV1 and TRPV4 channels in retinal angiogenesis". Thesis, Queen's University Belfast, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709849.
Pełny tekst źródłaSinharoy, Pritam. "Cross Talk Between TRPA1 and TRPV1 Ion-Channels: Role of Nitric Oxide". Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1467381679.
Pełny tekst źródłaChen, Lan [Verfasser]. "Functional TRPV1 and TRPV4 channels in the murine renal vasculature / Lan Chen". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2017. http://d-nb.info/1148425926/34.
Pełny tekst źródłaSUGIHARA, YASUO, MINORU UEDA, HIDEYUKI NAKASHIMA, KENJIRO NAGAMINE, HISASHI HATTORI, NORIYUKI OZAKI i KATSUNORI HIRONAKA. "INVOLVEMENT OF GLIAL ACTIVATION IN TRIGEMINAL GANGLION IN A RAT MODEL OF LOWER GINGIVAL CANCER PAIN". Nagoya University School of Medicine, 2014. http://hdl.handle.net/2237/20551.
Pełny tekst źródłaFernandes, Maria Antionetta. "An investigation of the roles of TRPV1, TRPA1 and hydrogen sulfide in thermoregulation". Thesis, King's College London (University of London), 2015. http://kclpure.kcl.ac.uk/portal/en/theses/an-investigation-of-the-roles-of-trpv1-trpa1-and-hydrogen-sulfide-in-thermoregulation(811086d3-46c1-4f3f-9288-131bebf36431).html.
Pełny tekst źródłaGrace, Megan Stacey. "Investigating the role of TRPA1 and TRPV1 ion channels in the cough reflex". Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/14571.
Pełny tekst źródłaColton, Craig K. "TRPV3 is a polymodal receptor". Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1164046830.
Pełny tekst źródłaEL, Andaloussi-Lilja Johanna. "Activation and regulation of TRPV1 : studies in recombinant human neuroblastoma TRPV1-SHSY5Y cells /". Stockholm : Department of Neurochemistry, Stockholm University, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-30182.
Pełny tekst źródłaAt the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: In press. Paper 4: In press. Härtill 4 uppsatser.
Ibarra, Yessenia Michelle. "Characterization of human TRPA1 and TRPV1 channels in response to naturally occurring defensive compounds". Thesis, Harvard University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3566933.
Pełny tekst źródłaThe transient receptor potential channels, ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1), are non-selective cation-permeable channels that have retained their function as chemical sensors since their first appearance in metazoan species several hundred million years ago. In vertebrates, TRP channels have evolved multiple functions which make it difficult to understand exactly how they transmit signals to the brain that are interpreted very differently. For example, TRPA1 and TRPV1 are sensitive to various chemicals and activation of these channels produce sensations with opposing effects. Pain is felt when TRPV1 is activated by spider toxins, but activation by plant cannabidiol results in a pain-relieving sensation. Similarly, TRPA1 activation by delta-tetrahydrocannabinol is reported to relieve symptoms of pain, but TRPA1 activation by the active ingredient in wasabi results in a repulsive or noxious sensation. Much of what we know about TRPA1 and TRPV1 comes from the use of plant products or exposure to substances that cause or alleviate pain and inflammation. In this study, whole-cell voltage clamp recordings of heterologously expressed human TRPA1 and human TRPV1 were tested for sensitivity to a hallucinogenic plant compound, salvinorin A and an arthropod-defensive compound, para-benzoquinone. Neither compound has yet been reported to activate TRP channels but both are known to be involved in pain and inflammation signaling in humans. I show that the arthropod compound, para-benzoquinone, activates and desensitizes TRPA1 in a cysteine-dependent manner, but activation of TRPV1 is not dependent on cysteine reactivity. Although salvinorin A is known to be a potent agonist of the kappa-opioid and cannabinoid receptors, here I show that it also acts as a highly potent agonist of both TRPA1 and TRPV1. Its interaction with TRP channels may contribute to its antinociceptive effects in behavioral studies with animals that are reported to be independent of opioid signaling.
DEMARTINI, CHIARA. "The role of TRPA1 and TRPV1 channels in trigeminal pain: data from animal models". Doctoral thesis, Università degli studi di Pavia, 2018. http://hdl.handle.net/11571/1214824.
Pełny tekst źródłaExperimental and clinical observations pointed out a critical involvement of transient receptor potential (TRP) channels, particularly TRPA1 and TRPV1, in trigeminal pain and associated symptoms, including hyperalgesia and allodynia. In this study the role of TRP channels was investigate in two animal models of diseases related to the trigeminal system: migraine and trigeminal neuropathic pain (TNP). TRPA1 and TRPV1 antagonists (ADM_12 and AMG9810 respectively) were used in the nitroglycerin (NTG)-induced hyperalgesia at the trigeminal level induced by means of the orofacial formalin test, a well validated animal model of migraine. The behavioral effects of AMG9810 gave inconclusive results, probably because its effect was confounded by the vehicle used. Nonetheless, it appears that TRPV1 channels are somehow involved in NTG-induced trigeminal hyperalgesia, since the TRPV1 mRNA levels were found to be strongly increased after NTG injection in medulla, cervical spinal cord and trigeminal ganglia (TG). NTG also up-regulated the mRNA levels of TRPA1, c-fos, calcitonin gene-related peptide (CGRP) and Substance P (SP) in the same areas. Those transcripts, but TRPV1, were reduced after ADM_12 treatment, which abolished the NTG-induced trigeminal hyperalgesia. The increased availability of nitric oxide after NTG promotes the formation of pro-inflammatory agents which can activate and/or sensitize nociceptors by means of TRPA1 and TRPV1 channels, causing the release of CGRP and SP. Although no differences in CGRP and SP protein expression were found at nucleus trigeminalis caudalis (NTC) level, the increased transcripts may reflect compensatory mechanisms aimed at reintegrating CGRP and SP stores depleted after NTG administration. It is possible that ADM_12 caused a reduction of Ca2+ influx through TRPA1 channels, which in turn interfered with the cascade of second-messenger molecules and with the Ca2+-interacting proteins, ultimately preventing NTG-induced inflammatory pathways. For TNP, the role of TRPA1 channels (by means of ADM_12) was investigated by evaluating mechanical allodynia in a model of chronic constriction injury of the infraorbital nerve (IoN-CCI). The IoN-CCI rats showed a hyperresponsiveness (4 weeks after surgery) at the ipsilateral side that reflects a condition of mechanical allodynia, and a significant increase in TRPA1, TRPV1, CGRP and SP mRNA expression levels. Although a tendency towards a decrease was seen in the ipsilateral compared to the contralateral side in the IoN-CCI rats, no significant differences in CGRP and SP protein expression at the NTC level were seen. However, their transcripts were highly increased in the central areas containing the NTC, as well as the TG ipsilateral to the IoN ligation. Both the allodynic response and the increased mRNA levels of operated rats were abolished after ADM_12 treatment. Probably, the blockade of TRPA1 channels located on the trigeminal afferents prevented neuropeptides release thus resulting in a reduced neurogenic inflammation and the nociceptors sensitization. Contrary to the migraine model, ADM_12 reduced transcript levels of both TRPs in IoN-CCI rats. Thus, ADM_12 appears to be a specific antagonist for TRPA1 in migraine pain, but in TNP it seems to act also on TRPV1. Probably, the damage induced by the nerve injury lead to a re-organization in expression and nature of the channels that made ADM_12 able to block TRPV1 channels. Since TRPA1 and TRPV1 are functionally linked, ADM_12 could have a direct effect on TRPA1 and an indirect effect on TRPV1 channels. In conclusion, TRPA1 blockade might be useful in the treatment of these trigeminal pain disorders. Moreover, our data suggest an important role also for TRPV1 channels, which could be differently involved depending on the type of pain. Further exploration on the mechanisms underlying the antinociceptive effects of these TRPs should improve our understanding of trigeminal pain processing.
Cao, Deshou. "Role of Transient Receptor Potential (TRP) Channels in Nociception". OpenSIUC, 2009. https://opensiuc.lib.siu.edu/dissertations/71.
Pełny tekst źródłaLeonelli, Mauro. "Receptores vanilóides TRPV1 na retina". Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/42/42137/tde-22072011-131242/.
Pełny tekst źródłaTRPV1 expression in the developing retina begins before retinal sinaptogenesis. TRPV1 blockade reduced the normal apoptosis in this period, and MAPK signaling seems to be involved in this process. In the adult retina, TRPV1 are expressed in neuronal, endothelial and microglial cells. The activation of those receptors is potentially cytotoxic, and glutamate release and further excitotoxicity and nitrosative stress might be also involved. Axotomized retinal ganglion cells were sensitized to TRPV1 citotoxicity, but TRPV1 antagonism, both in vitro and in vivo, did not reduce the loss of ganglion cell after axotomy. Our results suggest that TRPV1 receptors are involved in synaptic function and homeostatic control in the retina. Moreover, TRPV1 seems to be indirectly involved in cellular degeneration that follows the section of retinal ganglion cell axons.
Goswami, Chandan. "Identification of tubulin as a TRPV1-interacting protein and functional characterization of TRPV1-cytoskeleton regulation". [S.l.] : [s.n.], 2006. http://www.diss.fu-berlin.de/2006/315/index.html.
Pełny tekst źródłaRosano, Giulio. "Structure-function studies of TRPV1 alcohol modulation". Master's thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amslaurea.unibo.it/19298/.
Pełny tekst źródłaSchwarz, Holger Jens [Verfasser], i Bela [Akademischer Betreuer] Szabo. "Die Rolle des TRPV1-Rezeptors im Cerebellumcortex". Freiburg : Universität, 2016. http://d-nb.info/1119806062/34.
Pełny tekst źródłaPritchard, Sara. "Modulation of TRPV1 function in sensory neuropathy". Thesis, University of Hertfordshire, 2015. http://hdl.handle.net/2299/15360.
Pełny tekst źródłaSaffran, Alexander. "Activation of TRPV1 by Capsaicin Regulates ENaC". VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5544.
Pełny tekst źródłaHadrovic, Banina. "A study of TRPV1 and TRPV4 ion channels in the beta cells by using fura-2 based microfluorometry". Thesis, Mälardalen University, School of Sustainable Development of Society and Technology, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-7350.
Pełny tekst źródłaThe calcium ion (Ca2+) is an important ion that regulates many cellular functions including exocytosis, contraction of muscles, neural functions, fertilization and cell division. In the plasma membrane of cells there are different Ca2+ channels, including the transient receptor potential (TRP) family of cation channels. The TRP channels are activated by physical stimuli like temperature, stretch, osmolality, and also various ligands. These channels are divided into seven subfamilies, namely TRPC, TRPV, TRPM, TRPML, TRPA, TRPP, and TRPN.
TRP channels can regulate the cytoplasmic free Ca2+ concentration ([Ca2+]i) and are therefore important for research of insulin secretion from beta (β) cells. With TRP research new and more effective treatment methods for people with diabetes can be developed. People with type 2 diabetes have a decreased insulin secretion from beta (β) cells, in response to glucose. Cytoplasmic free Ca2+ concentration ([Ca2+]i) is important for insulin secretion. It is therefore desirable to find compounds that can increase [Ca2+]i in pancreatic β cells and thereby increase insulin secretion.
The aim of this project was to investigate whether pancreatic β cells express TRPV1 and TRPV4 ion channels. If the channels are expressed in β cells the [Ca2+]i can be increased by identifying substances that stimulate TRPV1 and TRPV4 channels. The results can then be used for providing better treatment for patients with diabetes type 2. Insulinoma cells from rat (S5 cells) were used as a model for β cells. [Ca2+]i was measured from single fura-2 loaded S5 cells by ratiometric microfluorometry. To test whether TRPV1 is expressed,
N-(4-hydroxyphenyl)-Arachidonoylamide (AM404) and [5-hydroxyl-1-(4-hydroxy-3-methoxyphenyl)decan-3-one] ([6]-gingerol) were used. To test whether TRPV4 was expressed, a TRPV4-selective agonist 4alpha-Phorbol 12,13-Didecanoate namely 4α–PDD was used.
The two agonist of TRPV1, AM404 and [6]-gingerol increased [Ca2+]i . Capsaicin a classical activator of TRPV1 used as a control also increased [Ca2+]i . These increases were inhibited by capsazepine, a specific blocker of TRPV1. 4α–PDD, a specific agonist of TRPV4 also increased [Ca2+]i. These results suggest that S5 cells express both TRPV1 and TRPV4 channels and that AM404, [6]-gingerol and 4α–PDD are potential substances for increasing the insulin secretion from β cells.
Kalciumjonen (Ca2+) är en viktig jon och förmedlar signaler i processer som cellutsöndring, muskelkontraktion, nervfunktion, fertilisering och celldelning. I cellers plasmamembran finns det olika sorters Ca2+ -kanaler, inklusive transient receptor potential (TRP) jonkanalerna. TRP kanalerna aktiveras av fysisk stimulans, så som temperatur, utsträckning, osmolalitet men också av olika ligander. TRP kanalerna är indelade i sju underfamiljer, TRPC, TRPV, TRPM, TRPML, TRPA, TRPP,och TRPN.
TRP kanalerna reglerar den fria Ca2+ koncentrationen ([Ca2+]i) i cytoplasman och är därmed viktiga för forskning inom insulinutsöndringen från beta (β) celler. Med denna forskning kan nya och effektivare behandlingsmetoder för personer med diabetes utvecklas. Personer med typ 2 diabetes har bl.a. en minskad insulinfrisättning i beta (β) celler som orsakar en glukosökning i blodet. Den fria Ca2+ -koncentrationen ([Ca2+]i) i cytoplasman är viktig för insulinfrisättningen. Det är därför önskvärt att hitta kemiska föreningar som kan bidra till en ökning av [Ca2+]i i bukspottkörtelns β celler och därmed också ge en ökad insulinfrisättning.
Målet med detta projekt har varit att undersöka om β celler från bukspottkörtel uttrycker jonkanalerna TRPV1 och TRPV4. Om β celler uttrycker dessa kanaler kan [Ca2+]i i cytoplasman ökas genom att identifiera substanser som stimulerar just TRPV1 och TRPV4 kanaler. Resultaten kan användas för att bidra med bättre behandling till diabetespatienter med typ 2 diabetes. Tumoriserade celler från råtta (S5) användes som modell för β celler. [Ca2+]i mättes från enskilda fura-2 laddade S5 celler med hjälp av ett ratiometriskt mikrofluorometriskt system. För att undersöka om TRPV1 finns testades ämnena N-(4-hydroxyphenyl)-Arachidonoylamide (AM404) och [5-hydroxyl-1-(4-hydroxy-3-methoxyphenyl)decan-3-one] ([6]-gingerol). För att undersöka om TRPV4 finns användes det TRPV4-specifika ämnet (4alpha-Phorbol 12,13-Didecanoate)
4α–PDD.
De båda TRPV1 agonisterna AM404 och [6]-gingerol inducerade en ökning i [Ca2+]i. Capsaicin som är en klassisk TRPV1 agonist ökade också [Ca2+]i och användes som kontroll. Alla dessa koncentrationsökningar inhiberades av capsazepine, som är en TRPV1- antagonist. 4α–PDD som är en specifik TRPV4 agonist ökade också [Ca2+]i.
Resultaten tyder på att S5 cellerna uttrycker både TRPV1 och TRPV4 kanaler samt att AM404, [6]-gingerol och 4α–PDD är alla substanser med potential att öka insulinfrisättningen från bukspottkörtelns β celler.
Niedermirtl, Florian [Verfasser], i Carla [Akademischer Betreuer] Nau. "Das intravenöse Anästhetikum Propofol aktiviert nozizeptive Neurone über TRPA1-, TRPV1- und GABAA-Rezeptoren / Florian Niedermirtl. Betreuer: Carla Nau". Erlangen : Universitätsbibliothek der Universität Erlangen-Nürnberg, 2011. http://d-nb.info/1018309101/34.
Pełny tekst źródłaWong, Benjamin. "Functional roles of different TRPV1 populations in calcium signalling of rat sensory neurons and HEK 293 cells expressing rat TRPV1". Thesis, University of Hertfordshire, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.632998.
Pełny tekst źródłaLeffler, Andreas. "TRPV1 ist ein polymodaler Rezeptor von nozizeptiven Spinalganglienzellen". [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972880216.
Pełny tekst źródłaHanack, Christina [Verfasser]. "Proteomics reveal insights into TRPV1 function / Christina Hanack". Berlin : Freie Universität Berlin, 2014. http://d-nb.info/1050978390/34.
Pełny tekst źródłaPaïta, Lucille. "Caractérisation du canal cationique TRPV1 dans les cardiomyocytes". Thesis, Lyon, 2016. http://www.theses.fr/2016LYSE1329/document.
Pełny tekst źródłaAcute myocardial infarction (MI), a leading cause of morbidity and mortality worldwide, is the irreversible death of heart muscle secondary to ischemia. This ischemia, i.e. oxygen and nutrients deprivation, triggers a reticular stress disrupting the Ca2+ balance of the cardiac cell. Several Ca2+ pumps and channels located at the sarcolemma or at the reticulum membrane are key players in this maintenance of Ca2+ homeostasis. Among them, we find passive leak channels, such as TRPs and little is known about their precise role in MI.TRPV1 represents a non-selective cation channel that is activated by capsaicin, pH and noxious heat. In skeletal muscle, we previously demonstrated that TRPV1 is located in the longitudinal part of the SR and respond to pharmacological and physiological activations (Lotteau et al., 2013). We questioned here whether TRPV1 might have a similar role in heart physiology. Biochemical analysis and intracellular Ca2+ measurements were performed on cardiomyocytes from wild-type and TRPV1-KO mice. Our in vitro results show that: (i) TRPV1 is expressed in cardiac cells; (ii) an increase in intracellular calcium concentration ([Ca2+]i) is elicited under TRPV1 activation; (iii) TRPV1 could be a direct target of isoflurane. In parallel, our in vivo results indicate that a pharmacological preconditioning by isoflurane decrease the infarct size, probably though activation of TRPV1. According to the fact that TRPV1 activity can be modulated by a lot of pharmacological molecules, TRPV1 may serve as therapeutic target to reduce the infarct size. Most of published data have already evidenced this TRPV1 cardioprotective role in the peripheral heart system. The aim of the present work is to describe how TRPV1 channels behave in adult cardiomyocytes
Jorge, Carolina Ocanha 1990. "Envolvimento dos receptores TRPV1 e TRPA1 na hiperalgesia muscular induzida pela contração isométrica sustentada no músculo gastrocnêmio de ratos". [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/244490.
Pełny tekst źródłaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Aplicadas
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Resumo: A dor musculoesquelética é um importante problema de saúde mundial. Dentre todos os tipos de dor, àquela induzida pela contração isométrica sustentada está relacionada com os movimentos corporais nas atividades da vida diárias e apresenta um alto impacto socioeconômico. Apesar da sua relevância clínica, os mecanismos moleculares envolvidos no desenvolvimento da dor muscular induzida pela contração isométrica sustentada são pouco conhecidos. Portanto, o objetivo deste estudo foi avaliar o envolvimento dos receptores TRPV1 e TRPA1 na hiperalgesia muscular mecânica induzida pela contração isométrica sustentada no músculo gastrocnêmio de ratos machos, da linhagem wistar. O antagonista seletivo do receptor TRPV1, AMG9810, reduziu significativamente a hiperalgesia muscular mecânica induzida pela contração isométrica sustentada quando administrado no músculo gastrocnêmio ipsilateral, mas não no contralateral. A administração intratecal de AMG9810 apresentou a mesma resposta. Similar ao TRPV1, a administração intramuscular e intratecal do antagonista seletivo do receptor TRPA1, HC030031, reduziu significativamente a hiperalgesia muscular induzida pela contração isométrica sustentada. No entanto, não foi observado modificação da expressão proteica dos receptores TRPV1 e TRPA1 no tecido muscular após a contração isométrica sustentada. Os dados sugerem que os receptores TRPV1 e TRPA1 expressos no músculo gastrocnêmio e corno dorsal da medula espinhal estão envolvidos na hiperalgesia muscular mecânica induzida pela contração isométrica sustentada em ratos. Sugerimos, portanto, que os receptores TRPV1 e TRPA1 co-expressos nas fibras aferentes primárias trabalhem juntos para ativar os nociceptores das fibras aferentes durante a contração isométrica sustentada. Além disso, nós sugerimos que os receptores TRPV1 e TRPA1 sejam potenciais alvos para o controle da dor muscular inflamatória
Abstract: Musculoskeletal pain is an important health issue in the world. Among the kinds of muscle pain, the one induced by sustained isometric contraction is associated with body movements of the daily life and has a high socio-economic impact. Despite its clinical relevance, the molecular mechanisms involved in the development of muscle pain induced by sustained isometric contraction are poorly understood. Therefore, the aim of this study was to evaluate the involvement of TRPV1 and TRPA1 receptors in the mechanical muscle hyperalgesia induced by sustained isometric contraction of the gastrocnemius muscle of rats. The selective TRPV1 receptor antagonist AMG 9810 reduced the mechanical muscle hyperalgesia induced by sustained isometric contraction when administered in the ipsilateral but not in the contralateral gastrocnemius muscle. Also, the intratecal administration of AMG9810 reduced the same response. Similar to TRPV1, intramuscular and intrathecal administration of selective TRPA1 receptor antagonist HC030031 reduced the mechanical muscle hyperalgesia induced by sustained isometric contraction. Finally, the sustained isometric contraction did not modify the protein expression of TRPV1 and TRPA1 receptors in muscle tissue. We concluded that TRPV1 and TRPA1 receptors expressed in gastrocnemius muscle and spinal cord dorsal horn are involved with the mechanical muscle hyperalgesia induced by sustained isometric contraction in rats. We suggest that TRPV1 and TRPA1 receptors co-expressed in primary afferent fibers work together to activate nociceptive afferent fibers during sustained isometric contraction. Also, we suggest that TRPV1 and TRPA1 receptors are potential target to control inflammatory muscle pain
Mestrado
Biodinâmica do Movimento Humano e Esporte
Mestra em Ciências da Nutrição e do Esporte e Metabolismo
Gu, C. "Signalling pathways underlying sensitization of TRPV1 by RET receptors". Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599771.
Pełny tekst źródłaCABRAL, Layla Dutra Marinho. "Influência do receptor vanilóide tipo 1 (TRPV1) na endotoxemia". Universidade Federal de Alfenas, 2016. https://bdtd.unifal-mg.edu.br:8443/handle/tede/997.
Pełny tekst źródłaBacterial endotoxin presence in the bloodstream is associated with the onset and maintenance of sepsis, complex and heterogeneous condition that promotes the release of inflammatory mediators, which lead to changes in the central nervous system and subsequent unbalanced inflammatory immune response, with consequent multiple organ failure. The TRPV1 receptor, in turn, participate in the modulation of different systems and can influence physiological processes impaired by inflammation, and so represent a potential therapeutic target. The aim of the study was to evaluate the involvement of TRPV1 receptors in acute lung injury/ acute respiratory distress syndrome (ALI/ARDS) and in the sickness behavior induced by endotoxin, with the blockade by capsazepine (CPZ) in mice. Regarding the ALI/ARDS, animals had the disease induced by LPS 5.0mg/kg with simultaneous application of CPZ and were analyzed after 24 hours. Reduced resistance of the system and tissue was observed, in addition to decreased alveolar collapse by the blockade of TRPV1 receptors, showing a modulation by these receptors in the ALI/ARDS. Regarding sickness behavior, animals received CPZ administration 30 minutes before application of LPS 200 μg/kg, and after 2 hours were submitted to the behavioral tests and blood and tissues collection. The administration of blocker attenuated the anxious and depressive-like effects, the increased body temperature and the c-fos expression in some brain areas induced by LPS. However, CPZ did not promote changes in mobility, food intake, weight gain, plasma levels of cytokines and protein expression in the hippocampus and hypothalamus. These results suggest the involvement of TRPV1 receptors in the modulation of sickness behavior, in regulating body temperature and respiratory mechanics after immune challenge.
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Rossato, Mateus Fortes. "Eriodictiol: um flavonóide antagonista do receptor trpv1 com atividade antioxidante". Universidade Federal de Santa Maria, 2010. http://repositorio.ufsm.br/handle/1/11134.
Pełny tekst źródłaThe transient receptor potential vanilloid 1 (TRPV1) is a calcium permeable channel responsible for the transduction and modulation of acute and chronic pain signaling, being a potential target for treatment of different pain disorders. In spite of that, AMG517, a TRPV1 antagonist, presents several clinical limitations, such as the development of severe hypertermia. The aim of this study was to investigate the possible interaction of the flavonoid eriodictyol with the TRPV1 receptor and its putative antinociceptive and hyperthermic effect. Eriodictyol was able to displace the [3H]-resiniferatoxin binding (IC50 = 47 (21 - 119) nM) and to inhibit the calcium influx mediated by capsaicin (IC50 = 44 (16 125) nM), suggesting that eriodictyol acts as a TRPV1 antagonist. Moreover, eriodictyol induces antinociception in the intraplantar capsaicin test, with maximal effect of 49±10 and 64±4% of inhibition for oral (ED50 = 2 (1-5) mg/kg) and intrathecal (ED50 = 2 (1-3) nmol/site) routes, respectively. Concomitantly, eriodictyol did not induce any alteration on body temperature or locomotor activity. Orally administered eriodictyol (4.5 mg/kg) prevented the nociception induced by intrathecal injection of capsaicin (72±6% of inhibition), the non-protein thiol loss and the 3-nitrotyronise (3-NT) formation induced by capsaicin in spinal cord. Eriodictyol (4.5 mg/kg, p.o.) also reduced the thermal hyperalgesia (100% of inhibition) and mechanical allodynia (62±9% of inhibition) elicited by complete Freund s adjuvant (CFA) paw injection. In conclusion, Eriodictyol acts as an antagonist of TRPV1 receptor and an antioxidant, inducing antinociception without some side effects and limitations expected for TRPV1 antagonists, as hyperthermia.
O receptor de potencial transiente vanilóide 1 (TRPV1) é um canal iônico permeável a cátions ativado por uma série de estímulos nocivos, como calor, acidificação e agentes irritantes como a capsaicina. Este receptor é responsável pela detecção e transmissão da dor aguda e crônica. Devido a isso, substâncias que modulem a atividade deste receptor apresentam um potencial clínico para o tratamento da dor. Assim, este trabalho objetiva a possível interação do flavonóide eriodictiol com o receptor TRPV1. Inicialmente, observamos que o eriodictiol foi capaz de deslocar o radioligante [3H]-resiniferatoxina, em ensaio de união específica, do receptor TRPV1 com uma concentração inibitória 50% (IC50) de 46.9 (20.70 - 118.9) nM. Ao mesmo tempo, o eriodictiol também inibiu o influxo de cálcio estimulado por capsaicina com IC50 de 44,4 (15,6 125,1) nM, sugerindo que este aja como um antagonista do receptor. Além disso, também observamos que o eriodictiol induz antinocicepção no teste da capsaicina intraplantar com efeito máximo de 49,0±10.5 e 63,9±4.0 % de inibição máxima para o tratamento oral e intratecal, respectivamente, e com uma dose efetiva 50% (DE50) de 2,4 (1,0 5,5) mg/kg 2,2 (1,6 2,9) nmol/site, respectivamente. Além disso, não observamos alterações na atividade locomotora ou temperatura corporal dos animais. A administração oral de eriodictiol também foi capaz de prevenir a nocicepção induzida por capsaicina intratecal (71,7±5,7 % de inibição). Ao mesmo tempo, o eriodictiol também aboliu a hiperalgesia térmica e reduziu a alodínia mecânica (62,4±9,2 %) induzidas por adjuvante completo de Freund. Da mesma forma, o eriodictiol também preveniu totalmente a diminuição de tiois não protéicos e formação de 3-nitrotirosina (3-NT) espinhais induzidas por capsaicina, ao passo que apresentou atividade antioxidante direta no texto de neutralização do radical ABTS. Em conclusão, nossos resultados mostram que o eriodictiol age como um antagonista do receptor TRPV1, com atividade antioxidante, induzindo antinocicepção sem os efeitos colaterais e limitações esperados para antagonistas do receptor TRPV1.
Kiasalary, Reineh Zahra. "Anatomical and functional studies on TRPV1- expressing primary sensory neurons". Thesis, Queen Mary, University of London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.420426.
Pełny tekst źródłaSadofsky, Laura Rachel. "Molecular pharmacology of the capsaicin receptor (TRPV1) in the airways". Thesis, University of Hull, 2005. http://hydra.hull.ac.uk/resources/hull:8630.
Pełny tekst źródłaBhattacharjee, Anupam. "The biophysics and pharmacology of native and recombinant TRPV1 receptors". Thesis, King's College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.409218.
Pełny tekst źródłaPaule, Cleoper. "Molecular bases underlying the sensitivity of the capsaicin receptor TRPV1". Thesis, Imperial College London, 2010. http://hdl.handle.net/10044/1/6144.
Pełny tekst źródłaSaunders, Cecil James. "The respiratory response of Trpv1 knockout mice to trigeminal irritants". Winston-Salem, NC : Wake Forest University, 2008. http://dspace.zsr.wfu.edu/jspui/handle/10339/37483.
Pełny tekst źródłaTessier, Nolwenn. "Rôle du canal calcique TRPV1 dans l’ischémie-reperfusion du myocarde". Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1165.
Pełny tekst źródłaDuring myocardial infarction, both I/R cause irreversible myocardial injuries. Among the cellular damages, calcium dysregulation occurs leading to cell death. To improve the recovery from I/R episodes, remote, pre- and post-conditioning are recognized to be cardioprotective. In particular, some strategies based on molecules acting on the TRPV1 channels have been used. The aim of our work is to better understand TRPV1 role in cardioprotection. We have recently demonstrated that TRPV1 is expressed and functional in adult mouse cardiomyocytes. In order to perform live imaging with genetic probes, an alternative model to cardiomyocytes was used in the present work: H9C2 cells. Thanks to Western blot and confocal microscopy, we first showed that TRPV1 is expressed in H9C2 and seems to be localized at endoplasmic reticular (ER) plasma membrane. Secondly, we demonstrated that TRPV1 is a functional ER Ca2+ leak channel via cytoplasmic and reticular Ca2+ imaging (respectively with Fura-2 and ErGAP1). As ATP synthesis and cell fate are dependent of Ca2+ exchanges between ER and mitochondria, we have analyzed the role of TRPV1 in the mitochondrial [Ca2+] using R-GECO probe. We observed that pharmacological TRPV1 modulation increases both cytosolic and mitochondrial Ca2+ contents by at least 20%. Finally, we performed hypoxia-reoxygenation sequences and we evaluated cell death by flow cytometry. We showed that TRPV1 activation has heterogeneous effects on cell viability, whereas TRPV1 inhibition always improves cell survival (at least by 22%). Precise and spatiotemporal Ca2+ release events from ER to mitochondria are required to initiate or to regulate many processes like the balance between cell death/cell survival. In the present study, we show that TRPV1 could be one of the channels involved in Ca2+ exchanges between ER and mitochondria, and that H9C2 is a valuable model to evaluate the role of TRPV1 in Ca2+ fluxes during I/R
Hua, Pierce. "Characterization of a novel pre-pore loop antibody against rat TRPV1". Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111948.
Pełny tekst źródłaSharif, Naeini Reza. "Contribution of the Trpv1 gene to the physiology of supraoptic neurons". Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111867.
Pełny tekst źródłaKasper, Christian [Verfasser]. "Die Modulation des TRPV1 Kanals durch das Adapterprotein ARMS / Christian Kasper". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2018. http://d-nb.info/1160514763/34.
Pełny tekst źródłaBonacin, Yuri da Silva. "Expressão e quantificação de receptores vanilóides TRPV1 na dermatite digital bovina /". Jaboticabal, 2017. http://hdl.handle.net/11449/150352.
Pełny tekst źródłaCoorientador: Sérgio Britto Garcia
Banca: Deborah Penteado Martins Dias
Banca: Paulo Aléscio Canola
Resumo: A Dermatite Digital Bovina (DDB) constitui uma das principais causas de graus elevados de claudicação em bovinos leiteiros, em função da dor que estes animais aparentam frente ao estímulo nocioceptivo. A hiperalgesia em alguns casos de dor crônica está relacionada à expressão exacerbada de fibras dos receptores vaniloides TRPV1, podendo haver forte correlação com casos crônicos da DDB. No presente estudo foram utilizados 15 bovinos, fêmeas, da raça Holandesa Preto e Branco, com idades de 2 a 7 anos, em lactação com pico médio de 47,85 L, mantidos em regime "free-stall". Durante o casqueamento realizado na propriedade, as lesões da DDB foram identificadas e divididas em quatro grupos, referentes aos quatro estágios da doença (inicial M1, clássico M2, intermediário M3 e crônico M4). Foram coletadas biópsias por meio de "punch" cutâneo (4mm). Além das lesões foram coletadas amostras de pele sadia de cada animal. Priori às biopsias realizou-se a dimensionamento das lesões, para média comparativa entre os estágios. Os fatores predisponentes ao aparecimento de lesões (idade, número de partos e pico de lactação) foram considerados. As biopsias foram processadas em laboratório e colocadas frente à reação imunológica com anticorpos anti-TRPV1 (Chemicon -USA). Posteriormente as fibras imuno-marcadas nos quatro grupos e pele sadia foram contabilizadas e comparadas. As dimensões das lesões foram analisadas pelo método estatístico descritivo e possuíam média de comprimento e largura no es... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The Bovine Digital Dermatitis (BDD) is one of the main cause on high claudication levels at the dairy cattle, as a result of the pain that appear in those animal front of the nociceptive stimulus. Hyperalgesia in some chronic pain cases is related to the exacerbated expression of vanyloid TRPV1 fibers, and may have a hole on the chronic cases of BDD. In the present study, 15 Black and White Holstein cow was used, aged 2 to 7 years old, during lactation with mean peak of 47.85L, kept in the free-stall under the same diet. BDD lesions were identified and divided into 4 stages of the disease (initial M1, classic M2, intermediate M3 and chronic4), which skin are collected by dermal punch (4mm). In addition to the lesions, healthy skin samples were collected from each animal. Prior to the biopsies, the lesion dimensions were taken, for comparative average between the stages. Predisposing factors to the lesions appearance (age, number of births and lactation peak) were considered. The biopsies were processed at the laboratory and reacted with anti-TRPV1 antibodies (Chemicon -USA). The immuno-marked fibers in the four groups and healthy skin were counted and compared. The lesion dimensions were analyzed by descriptive statistical method and had a M1 mean length/ width on M1 of 5,60mm±3,20 x 4,4±1,34mm, M2 of 12,60±6,46mm x 14,4±8,87mm, M3 of 21,60±3,36mm x 17,20±6,61mm and M4 of 21,60±3,36mm x 24,57±7,32mm. The thickness mean value in M1 of 1.80 ± 1.09mm, M2 of 6.20 ± 2.16mm, M3 of 7.40 ± 6.54mm and M4 of 8.85 ± 4.14mm. The predisposing factors results were analyzed separately with the number of lesions by Pearson Correlation statistic method (p <0.05). There was difference between more lesion and birth numbers. TPV1 fiber counts were analyzed by logarithmic scale (p <0.05), with a significant difference between the M4 group (chronic stage of DDB) and the other groups.
Mestre
Mak, Stephanie Wai Yin. "Modulation of temperature sensitive ion channels TRPV1 and TRPM8 by Bradykinin". Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611520.
Pełny tekst źródłaSantos, Fabio Martinez dos. "Mobilização neural: avaliação molecular e comportamental em ratos Wistar após indução de dor neuropática". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/42/42131/tde-05102015-150313/.
Pełny tekst źródłaNeural mobilization technique (MOB) is a noninvasive method that demonstrated to be effective in reducing pain sensitivity in both clinical and research study. The present study aims to examine the effects of MOB in locomotors dysfunction, muscle strength, morphological changes in sciatic nerve and molecular changes induced by chronic constriction (CCI) of the sciatic nerve in Wistar rats. To analyze locomotors dysfunction we used the Sciatic nerve functional index (SFI). To analyze muscle strength, was used Biopac System. The nerve morphology was analyzed using electron microscopy and molecular changes through western blot assays. After MOB treatments, animals were euthanized and tissues such as, sciatic nerve, the posterior root ganglions (DRG L4-L6) and substance periaqueductal gray (PAG) were removed. The DRG were processed by western blot for detection of substance P (SP), transient receptor potential vanilloid type I (TRPV1) and opioids receptors (MOR, DOR, KOR). Regarding PAG, we analyze only opioids receptors. Our results demonstrated a full reversal of locomotors dysfunction-induced by CCI after MOB treatment and an increase of 172% on maximal tetanic muscle strength in animals treated with MOB when compared to the CCI group. Our studies on photomicrography of sciatic nerve showed an intense Wallerian degeneration process in CCI animals and an intense regeneration of myelinated fibers. In western blot assays, we identified, in DRG, an increase of SP and TRPV1 expression after CCI and a decrease of optical density after MOB treatment. Regarding opioid receptor, we did not identify statistical changes on DOR and KOR in DRG, but we observed an increased expression of MOR in CCI after MOB treatment group. In PAG analyses, we observed a decrease in DOR and KOR expression after MOB treatment when compare with CCI animals. On the other hand, we did not identify any changes on MOR receptor. Based on our findings, we suggest that treatment with neural mobilization technique it is able to reverses the locomotors dysfunction and increases maximum tetanic force of the tibialis anterior muscle after CCI. Furthermore, the same treatment was also able to induce a severe regeneration in the sciatic nerve after treatment. Still, we can suggest an important role of MOB in modulating SP and TRPV 1 expression. We suggest that antinociceptive effect induced by MOB technique can also be involved with descending pain inhibitory system resulting in inhibition of the transmission of afferent nociceptive stimulus and thereby reducing neuropathic pain because of the influence of MOB opioids in the PAG.
JÃnior, Roberto CÃsar Pereira Lima. "Antinociceptive effect of the mixture of pentacyclic triterpenes alpha- and beta- amyrin in models of visceral nociception in mice". Universidade Federal do CearÃ, 2005. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=4.
Pełny tekst źródłaProtium heptaphyllum March (Burseraceae), a medicinal plant commonly found in the Amazon and in the Northeast regions of Brazil, releases an oil-resin rich in pentacyclic triterpenes, such as the binary mixture of alpha- and beta- amyrin, that manifests antiinflamatory, antinociceptive and gastroprotective properties. This work was aimed to evaluate the antinociceptive effect of the alpha- and beta- amyrin mixture in the cyclophosphamide (400 mg/kg), acetic acid (0,6%, 10mL/kg, i.p.) and mustard oil-induced visceral nociception models in mice and to establish the likely mechanism(s) of action. In the cyclophosphamide-induced visceral pain model, pretreatment of mice with triterpene mixture at the oral doses of 10, 30 and 100 mg/kg significantly reduced (p<0.001) the pain-related behavioral expression time (59,7; 75,5 e 92,3%, respectively, versus the cyclophosphamide-treated group 12,25 +/- 2,98 min) in a dose-dependent manner. Suppression of visceral painârelated behaviors was also evidenced to the triterpenoid mixture (10 mg/kg) in the intraperitoneal acetic acid- and intracolonically injected mustard oil-induced test models of visceral nociception 50,4% e 61,1%, respectively compared to the acetic acid-treated group (42,33 +/- 3,78 abdominal constrictions/20 min) in the writhing test and to the control in the mustard oil (0,75%, 50 mcL/animal) experiment (39,28 +/- 3,26). In these tests, the maximal suppression of visceral pain was observed at 10 mg/kg. The possible mechanisms involved in the antinociceptive action of alpha- and beta- amyrin (10 mg/kg) were analyzed in the mustard oil-induced visceral pain model. In the evaluation of the opioid receptor involvement, both the triterpene mixture and morphine (5 mg/kg, s.c.) effectively inhibited (p<0.001) the number of pain-related behaviors, which could be significantly reversed by pretreatment of animals with an opioid antagonist naloxona (2mg/kg, i.p.), suggesting the opioid participation in the alpha- and beta- amyrin mechanism of action. In the study of the alpha2-adrenoreceptor involvement, the triterpene mixture as well as clonidine (0.1 mg/kg, i.p.), a known alpha2 agonist, inhibited (p<0.001) the nociceptive behavioral expression. However, when the animals were pretreated with yohimbine, an alpha2-adrenoreceptor antagonist, only the inhibitory action of clonidine was reversed, suggesting the non-participation of alpha2- adrenoreceptor in the antinociceptive action of alpha- and beta- amyrin. In the evaluation of TRPV1 receptor involvement, mice pretreated with either the alpha- and beta- amyrin, ruthenium red, a TRPV1 non-competitive antagonist, (3 mg/kg, s.c.) or their combination induced a significant and similar inhibition (p<0.001) of the number of nociceptive behaviors. The degree of inhibition with no potentiation or antagonism suggests that alpha- and beta- amyrin may act as a TRPV1 non-competitive antagonist, like ruthenium red. In order to evaluate a possible sedative, motor impairment and motor incoordination effects related to alpha- and beta- amyrin, the penthobarbitone-induced sleeping time, open-field and rota-rod tests were performanced, respectively. The data indicated that the treatment of animals with the alpha- and beta- amyrin mixture (10 mg/kg) was unable to cause sedation, motor impairment or motor incoordination effects (p>0.05), being even able to reverse (p<0.05) a mustard oil-induced motor impairment in the open field test. The results taken together strongly suggest the therapeutic potential of alpha- and beta- amyrin in oblitering visceral nociception through the mechanisms that involve the opioids and TRPV1 receptors.
O Protium heptaphyllum March. (Burseraceae), uma planta medicinal encontrada na regiÃo AmazÃnica e Nordeste do Brasil, produz uma resina rica em triterpenos pentacÃclicos, como a mistura binÃria alpha- e beta- amirina, que apresentam atividade antiinflamatÃria, gastroprotetora e antinociceptiva. Este trabalho objetivou investigar a atividade antinociceptiva de alpha- e beta- amirina em modelos de dor visceral induzida por ciclofosfamida, Ãcido acÃtico e Ãleo de mostrada em camundongos, alÃm dos possÃveis mecanismos de aÃÃo envolvidos. No modelo de nocicepÃÃo visceral induzida por ciclofosfamida (400 mg/kg, i.p.), a mistura de triterpenos nas doses de 10, 30 e 100 mg/kg, v.o., reduziu (p<0,001) de forma dose-dependente o tempo de expressÃo dos comportamentos relacionados à dor visceral (59,7; 75,5 e 92,3%, respectivamente, versus o controle ciclofosfamida 12,25 +/- 2,98 min). Realizou-se o estudo nos modelos de contorÃÃes abdominais induzidas por Ãcido acÃtico (0,6%, 10mL/kg, i.p.) e dor visceral induzida por Ãleo de mostarda (0,75%, 50 mcL/animal) intracolÃnico. Os resultados indicaram uma inibiÃÃo do nÃmero de comportamentos de dor expressos pelos animais, sendo o maior nÃvel de inibiÃÃo (p<0,001) encontrado na dose de 10 mg/kg da alpha- e beta- amirina 50,4% e 61,1% comparados respectivamente ao controle Ãcido acÃtico (42,33 +/- 3,78 contorÃÃes/20min) no teste de contorÃÃes abdominais e ao controle Ãleo de mostarda (39,28 +/- 3,26) no modelo de dor visceral por Ãleo de mostarda. Para o estudo do possÃvel mecanismo de aÃÃo de alpha- e beta- amirina foi utilizada a dose de 10 mg/kg da mistura de triterpenos no modelo de nocicepÃÃo por Ãleo de mostarda. Na avaliaÃÃo da participaÃÃo do sistema opiÃide, a mistura dos triterpenos e a morfina (5 mg/kg, s.c.) inibiram significativamente (p<0,001) o nÃmero de comportamentos de dor expressos, havendo uma reversÃo da antinocicepÃÃo (p<0,05) quando prÃ-tratados com naloxona (2 mg/kg, i.p.), sugerindo a participaÃÃo opiÃide no mecanismo da alpha- e beta- amirina. No estudo do envolvimento do sistema adrenÃrgico, a mistura de triterpenos e a clonidina (0,1 mg/kg, i.p.), um agonista alpha2-adrenÃrgico, inibiram (p<0,001) a expressÃo dos comportamentos nociceptivos. PorÃm, com o prÃ-tratamento com ioimbina, um antagonista alpha2, houve reversÃo (p<0,05) da antinocicepÃÃo induzida pela clonidina, mas nÃo da alpha- e beta- amirina, sugerindo o nÃo envolvimento deste receptor na antinocicepÃÃo da mistura de triterpenos. No estudo do envolvimento do receptor TRPV1, o prÃ-tratamento dos animais com alpha- e beta- amirina, vermelho de rutÃnio (3 mg/kg, s.c.), um antagonista nÃo competitivo deste receptor, ou com a combinaÃÃo da mistura de triterpenos com vermelho de rutÃnio, houve uma inibiÃÃo (p<0,001) semelhante, para todos os tratamentos, dos comportamentos de dor. A nÃo potencializaÃÃo, ou antagonismo, do efeito antinociceptivo de alpha- e beta- amirina pelo vermelho de rutÃnio sugere que a mistura atue como um antagonista nÃo-competitivo TRPV1. Para avaliar a existÃncia de um efeito sedativo, de um impedimento locomotor ou de uma incoordenaÃÃo motora, foram utilizados os testes do tempo de sono induzido por pentobarbital, teste do campo aberto e o teste do rota rod, respectivamente. Os dados indicaram que o tratamento com a mistura de triterpenos (10 mg/kg) nÃo induziu (p>0,05) sedaÃÃo, impedimento locomotor ou incoordenaÃÃo motora nos animais, sendo ainda capaz de reverter (p<0,05) o impedimento locomotor induzido pelo Ãleo de mostarda no teste do campo aberto. Em conjunto os dados revelaram a efetividade da mistura de alpha- e beta- amirina em modelos de nocicepÃÃo visceral possivelmente envolvendo receptores opiÃides e TRPV1.
Dias, MarÃlia Leite. "Atividade antinociceptiva da riparina IV: participaÃÃo dos receptores TRPV1, TRPM8, receptores glutamatÃrgicos e do Ãxido nÃtrico". Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=8632.
Pełny tekst źródłaA Riparina IV, uma alcamida sintetizada de Aniba riparia, foi testada em modelos animais padronizados de dor, bem como os possÃveis mecanismos de aÃÃo envolvidos. Foram utilizados camundongos Swiss (20-30g), e a Riparina IV foi administrada de forma aguda em todos os testes, nas doses de 25 e 50 mg/kg, por via oral. Foram utilizados os testes de contorÃÃes abdominais induzidas por Ãcido acÃtico; placa quente; teste da formalina; hipernocicepÃÃo mecÃnica induzida pela carragenina; teste da nocicepÃÃo induzida por capsaicina, cinamaldeÃdo, mentol; teste da nocicepÃÃo induzida por glutamato, bem como em modelos comportamentais que permitam excluir a possibilidade de uma atividade relaxante muscular ou induzir resultados falso-positivos nos modelos anteriores, tais como testes do campo aberto e rota Rod. Os resultados demonstraram que a Riparina IV possui uma atividade antinociceptiva no modelo de nocicepÃÃo visceral induzida por Ãcido acÃtico. A Riparina IV nÃo demonstrou atividade no modelo de nocicepÃÃo tÃrmica da placa quente. O prÃ-tratamento com a Riparina IV reduziu significativamente a nocicepÃÃo inflamatÃria induzida pela segunda fase da formalina, porÃm nÃo alterou a nocicepÃÃo neurogÃnica induzida pela primeira fase do teste da formalina. Os animais prÃ-tratados com a Riparina IV tambÃm exibiram uma reduÃÃo significativa na hipernocicepÃÃo mecÃnica induzida pela carragenina. Em relaÃÃo à participaÃÃo dos receptores de potencial transitÃrio (TRP), a Riparina IV demonstrou atividade nos modelos de nocicepÃÃo induzida pela administraÃÃo de capsaicina e mentol, porÃm nÃo apresentou atividade na nocicepÃÃo induzida por cinamaldeÃdo. TambÃm reduziu a nocicepÃÃo induzida pela administraÃÃo intraplantar de glutamato. Para o estudo dos mecanismos de aÃÃo da Riparina IV foi utilizada somente a dose de 50 mg/kg da substÃncia. Na avaliaÃÃo da participaÃÃo dos canais de potÃssio ATP-dependentes, o prÃ-tratamento com glibenclamida nÃo foi capaz de reverter a aÃÃo antinociceptiva da Riparina IV, descartando-se o seu envolvimento; da mesma forma, o prÃ-tratamento com ioimbina, um antagonista α2-adrenÃrgico, e pCPA, um depletor das reservas de serotonina, tambÃm nÃo foram capazes de reverter tal aÃÃo, nÃo havendo envolvimento com o mecanismo de aÃÃo da Riparina IV. O prÃ-tratamento com L-arginina, um precursor do Ãxido nÃtrico, reverteu a aÃÃo antinociceptiva da Riparina IV, sugerindo, em parte, a participaÃÃo da via do Ãxido nÃtrico no seu mecanismo de aÃÃo. Os resultados mostraram que essa substÃncia nÃo alterou a atividade locomotora no teste do campo aberto, nem diminuiu o nÃmero de quedas no teste do rota Rod, descartando a possibilidade de haver sedaÃÃo ou incoordenaÃÃo motora por parte da Riparina IV. Em sÃntese, os resultados demonstraram que a Riparina IV possui uma atividade em modelos animais de nocicepÃÃo, possivelmente envolvendo os receptores TRPV1, TRPM8, glutamatÃrgicos e a via do Ãxido nÃtrico.
Riparin IV, an alkamide synthesized from Aniba riparia, was tested in standard animal models of pain, as well as the possible mechanisms of action involved. It was used Swiss mice (20-30g), and Riparin IV was administred acutely in all tests, at the doses of 25 and 50 mg/kg, by gavage. It was used the tests of abdominal writhing induced by acetic acid, hot plate test, formalin test, mechanical hypernociception induced by carrageenan, nociception test induced by capsaicin, cinnamaldehyde and menthol, nociception test induced by glutamate, as well as models of behavior that ruled out the possibility of a muscle relaxing activity or induce false-positive results in previous models, such as the open field test and the rota Rod test. The results showed that Riparin IV has an antinociceptive activity at the model of visceral nociception induced by acetic acid. Riparin IV did not show any activity at the hot plate thermal nociception model. Pretreatment with Riparin IV reduced significantly the inflammatory nociception induced at the second phase of formalin test, but did not alter the neurogenic nociception induced at the first phase of formalin test. The animals pretreated with Riparin IV also exhibited a significant reduction at the mechanical hypernociception induced by carrageenan. Related to the participation of the Transient Potential Receptors (TRP), Riparin IV showed an activity at the models of nociception induced by capsaicin and menthol, but did not show any activity at the nociception induced by cinnamaldehyde. Also reduced the nociception induced by administration of glutamate at the rind paw. To study the mechanisms of action of Riparin IV, it was used only the dose of 50 mg/kg of the substance. At the evaluation of participation of the ATP-dependent potassium channels, pretreatment with glibenclamide was not able to reverse the antinociceptive action of Riparin IV, discharging its involvment; at the same way, pretreatment with yohimbine, an a2-adrenergic antagonist, and pCPA, a depletor of the serotonin reservations, were not able of reverse such action, not having any involvement with the mechanism of action of Riparin IV. Pretreatment with L-arginine, a precursor of Nitric Oxide, reversed the antinociceptive action of Riparin IV, suggesting, in part, the participation of nitric oxide pathway at the mechanism of action. The results showed that this substance did not alter the locomotor activity at the open field test, neither diminished the number of falls at the rota Rod test, discharging the possibility of sedation or incoordination by Riparin IV. In summary, the results showed that Riparin IV has an action in animal models of nociception, possibly involving the receptors TRPV1, TRPM8, glutamatergic receptors and the nitric oxide pathway.
Zhou, Bolu. "Activation Of Trpv1 Channel Contributes To Serotonin-Induced Constriction Of Mouse Facial Artery". ScholarWorks @ UVM, 2017. http://scholarworks.uvm.edu/graddis/754.
Pełny tekst źródłaVidal, Mosquera Miguel. "Chemical modulation of the nociceptive receptor TRPV1: Synthetic, biological and computational studies". Doctoral thesis, Universitat Ramon Llull, 2016. http://hdl.handle.net/10803/369846.
Pełny tekst źródłaEl canal iónico Receptor Vanilloide Tipo 1 (siglas en ingles TRPV1) se considera un importante integrador de diversas señales de dolor. De entre todos los productos que interaccionan con TRPV1, aquellos que bloquean la señal dolorosa de forma no competitiva han atraído el interés de los investigadores que trabajan en el campo. A partir de resultados previamente obtenidos para varios peptoides que mostraron actividad como antagonistas no competitivos de TRPV1 y que permitieron proponer una sencilla hipótesis farmacoforica que incluía un grupo catiónico y dos aromáticos idénticos, la presente tesis se centró en el diseño y preparación de productos con estructuras más rígidas, no peptoides, capaces de interaccionar con TRPV1 como bloqueadores no competitivos. La evaluación biológica de una colección de nuevos antagonistas y un estudio en profundidad in vitro e in vivo del compuesto más activo proporcionaron información sobre el modo de acción de estos compuestos. Entre diferentes alternativas consideradas, el esqueleto de 1,3,5-triazina fue seleccionado como el más adecuado para albergar los requisitos estructurales del farmacóforo propuesto. Se sintetizaron un total de 38 1,3,5-triazinas-2,4,6-trisubstituidas con estructuras químicamente diversas utilizando un procedimiento previamente optimizado. Un estudio por RMN combinado con cálculos teóricos permitió determinar que muchas de estas triazinas presentan diferentes conformeros en equilibrio en solución, derivados de la rotación de los enlaces que unen las tres cadenas laterales al anillo de triazina. Diez de de ellas resultaron especialmente activas, bloqueando el canal TRPV1 con valores de IC50 en el rango submicromolar. De entre las triazinas sintetizadas destaca el compuesto 46 por su elevada potencia (IC50 = 50 nM), encontrandose entre los bloqueadores de TRPV1 más potentes descritos hasta el momento. La triazina 46 presenta una actividad polimodal capaz de inhibir la activacion de TRPV1 por capsaicina y pH, una toxicidad reducida tanto en ensayos in vitro como in vivo y actúa de forma selectiva sobre TRPV1. En cuanto a su modo de acción, 46 actúa como un bloqueador de canal abierto que se une en una posición relativamente profunda dentro del poro acuoso del canal. Se han construido modelos 3D-QSAR empleando la técnica CoMSIA, que correlacionan las propiedades estructurales de la colección de compuestos sintetizados con su actividad. Estos modelos dan soporte a la hipótesis inicial sobre los determinantes estructurales de la actividad antagonista de TRPV1, y constituyen una herramienta para la predicción de la actividad de nuevos compuestos. Usando dichos modelos se predijo una actividad en el rango bajo micromolar para miembros de una familia de analogos basados en un esqueleto central de pirrolidina. La síntesis y evaluación de la actividad antagonista de TRPV1 de alguno de estos análogos confirmó las predicciones, validando dichos modelos 3D-QSAR y estableciendo dichos compuestos como un interesante punto de partida para el desarrollo de una nueva familia de antagonistas.
The ion channel Vanilloid receptor type 1 (TRPV1) is considered an important integrator of various pain stimuli. Among the products that interact with TRPV1, the ones blocking the “pain signal” in an uncompetitive manner have attracted the attention of researchers working in the field. Based on previously obtained results for several peptoid hits that showed activity as uncompetitive TRPV1 antagonists, and that allowed to propose a basic pharmacophoric hypothesis consisting on one cationic and two identical aromatic moieties, this thesis focused on the design and synthesis of new antagonists with a more rigid non-peptoid structure. Biological evaluation of a collection of new blockers and an in depth in vitro and in vivo study of the most active one provided knowledge about their mode of action. In addition, a 3D-quantitative structure-activity relationship study (3D-QSAR) allowed to generate models that explain the observed biological activity and can help to predict the activities of new compounds. The 1,3,5-triazine skeleton was selected as rigid non-peptoid scaffold that can hold the three required pharmacophoric features. A total of 38 2,4,6-trisubstituted-1,3,5-triazines were synthesized using an optimized procedure. An in depth NMR study combined with theoretical calculations allowed to determine that most of these triazines present different conformers in equilibrium in solution, derived from the rotation of the bonds that joint the three side chains to the triazine ring. Ten of those triazines were particularly active blocking TRPV1 with submicromolar IC50 values. Triazine 46 exhibited a remarkably high activity (IC50 = 50 nM) being one of the most potent TRPV1 blockers described. It behaves as a polymodal antagonist against capsaicin and pH activation signals, exhibiting a low toxicity profile both in vitro and in vivo. Concerning its mechanism of action, 46 acts as an open channel blocker that locates relatively deep within the aqueous channel pore. Statistically significant 3D-QSAR models were generated, using the CoMSIA methodology, for the anti-TRPV1 activity of the newly synthesized compounds. Those models reinforced the initial hypothesis on the structural requirements for uncompetitive TRPV1 antagonists and provided a quantitative tool that could help to predict the activity of new compounds. Using these models, an activity in the low micromolar range was estimated for a few members of a new family of pyrrolidine based TRPV1 antagonists. The synthesis and biological evaluation of some of them confirmed the activity prediction, further validating the 3D-QSAR models and establishing these pyrrolidine analogues as an interesting starting point for further development of new anti-TRPV1 compounds.
Hoffmeister, Carin Gorete Hendges. "PAPEL DO TRPV1 EM UM MODELO ARTICULAR DE GOTA AGUDA EM RATOS". Universidade Federal de Santa Maria, 2014. http://repositorio.ufsm.br/handle/1/3838.
Pełny tekst źródłaThe gout is an extremely painful type of arthritis. Despite the large number of drugs available for its treatment, they usually cause many adverse effects that limit their use. Then, further investigations are necessary for a better understanding the different mechanisms involved in gout. It was found previously that TRPV1 receptor, an ion channel modulated by various inflammatory mediators mediated edema and the nociceptive responses induced by subcutaneous injection of MSU in rats. In this plantar model, activation of TRPV1 depended largely on the activation of mast cells. Since the environments articular broadly differ as their cellular constituents, questioned the involvement of this receptor in a more reliable model with this clinical arthropathy. The aim of this study was to investigate the role of TRPV1 in a model of acute gout induced by intra-articular administration (i.a.) of crystals of monosodium urate (MSU) tíbio-tarsal articulation rats. It was observed that the antagonism of the TRPV1 receptor (by the selective antagonist SB366791), systemic knockdown (caused by treatment with resiniferatoxin subcutaneous injection a TRPV1 agonist) or axonal silencing (perineural injection a combination of capsaicin and QX-314) sensory fibers TRPV1-positive significantly prevented the pain-related behaviors (spontaneous nociception, heat hyperalgesia, and mechanical allodynia) and inflammation (edema, plasma extravasation, leukocyte infiltration and IL - 1β ) was caused by the administration of MSU. Additionally, we observed a significant increase in immunoreactivity of TRPV1 in articular tissue 4 hours after administration of MSU. Subsequently, we investigated the possibility role of NO, an endogenous activator of TRPV1 in this model. The administration of MSU induced an increase in the production of stable metabolites (NOx) emissions of nitric oxide (NO) exudates in the joint, which was inhibited by a selective inhibitor of nitric oxide synthase (NOS). In addition, the non-selective NOS inhibitor prevented the spontaneous nociception, edema and plasma extravasation, and leukocyte infiltration after MSU injection. Moreover it was found that the administration of a NO donor induced heat hyperalgesia and spontaneous nociception, but not mechanical allodynia and edema. The TRPV1 receptor antagonism prevented only the edema caused by that donor. Thus, these results suggest that TRPV1 plays a role in the development and maintenance of nociceptive and inflammatory responses triggered in the model of acute articular gout, but only edematogenic response appears to be mediated by TRPV1 activation by NO.
A gota é um tipo de artrite extremamente dolorosa. Apesar do grande número de fármacos disponíveis para seu tratamento. Muitos causam efeitos adversos que limitam seu uso. Maiores investigações são necessárias para um melhor entendimento dos diferentes mecanismos envolvidos na gota. Verificou-se previamente que o receptor TRPV1, um canal iônico modulado por vários mediadores inflamatórios, mediou as respostas nociceptiva e edematogênica induzidas pela injeção subcutânea de MSU em ratos. Neste modelo plantar, a ativação do TRPV1 dependeu amplamente da ativação de mastócitos. Sendo o ambiente articular amplamente diferenciado quanto a sua constituição celular, questionou-se o envolvimento deste receptor em um modelo mais fidedigno com a clínica dessa artropatia. O objetivo deste estudo foi investigar o papel do TRPV1 em um modelo de gota aguda, induzida pela administração intra-articular (i.a.) de cristais de urato monossódico (MSU) na articulação tíbio-tarsal de ratos. Observou-se que o antagonismo do receptor TRPV1 (pelo antagonista seletivo do receptor TRPV1 SB366791), a desfuncionalização sistêmica (causada pelo tratamento subcutâneo com resiniferatoxina) ou o silenciamento axonal (com a combinação periciática de capsaicina e QX 314) das fibras sensoriais TRPV1-positivas preveniram significativamente os comportamentos relacionados à dor (nocicepção expontânea, hiperalgesia ao calor e alodínea mecânica) e à inflamação (edema, extravasamento plasmático, infiltração de leucócitos e produção de IL-1β) causadas pela administração i.a. de MSU. Adicionalmente, observou-se um aumento expressivo da imunoreatividade do TRPV1 no tecido articular 4 horas após a administração do MSU. Posteriormente investigou-se a possibilidade do NO ser um ativador endógeno do TRPV1 neste modelo. Demonstrou-se que a administração i.a. de MSU induziu um aumento na produção de metabólitos estáveis (NOx) do óxido nítrico (NO) nos exsudatos articulares, o qual foi inibido pela administração i.a. de um inibidor não seletivo da óxido nítrico sintase (NOS). Além disso, o inibidor não seletivo da NOS preveniu a nocicepção espontânea, o edema e também o extravasamento plasmático, a infiltração de leucócitos. Por outro lado constatou-se que a administração i.a. de um doador de NO induziu nocicepção espontânea e hiperalgesia ao calor, mas não alodínea mecânica ou edema. O antagonismo do receptor TRPV1 preveniu somente o edema causado por esse doador. Assim, estes resultados sugerem que o TRPV1 exerce um papel relevante no desenvolvimento e manutenção das respostas nociceptiva e inflamatória desencadeadas no modelo articular de crise aguda de gota, porém, apenas a resposta edematogênica parece ser mediada pela ativação TRPV1 através do NO.