Dissertations / Theses on the topic 'P2Z receptors'
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Gargett, Caroline Eve, and mikewood@deakin edu au. "Studies of the human lymphocyte P2Z receptor and its activation of phospholipase D." Deakin University, 1997. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20060727.144101.
Full textMateos-Trigos, Gabriela. "P2 receptors (P2Y₁ and P2Y₁₂) of equine platelets." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620715.
Full textAlberto, Anael Viana Pinto. "Caracterização dos receptores P2 em eosinófilos de ratos e do poro associado ao receptor P2X7." Instituto Oswaldo Cruz, 2012. https://www.arca.fiocruz.br/handle/icict/6938.
Full textMade available in DSpace on 2013-09-20T15:33:03Z (GMT). No. of bitstreams: 1 Anael Viana Pinto Alberto.pdf: 4150812 bytes, checksum: 9ce0a5d780533302dcc603ae65f510fe (MD5) Previous issue date: 2012-10-31
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil
ATP e outros nucleotídeos são liberados para o meio extracelular por vias reguladas ou pela perda da integridade de membrana. Uma vez fora da célula, esses compostos podem ativar receptores P2: P2X (receptores ionotrópicos) e P2Y (receptores acoplados a proteínas G). Além disso, O receptor P2X7 é um importante membro da família P2X, já que sua ativação pode levar a abertura de um poro membranar que permite a passagem de moléculas de até 900 Da. Os eosinófilos são as principais células efetoras em respostas alérgicas e estão associados com diversos processos fisiológicos e patológicos. Nesse trabalho investigamos a expressão de receptores P2 e suas funções em eosinófilos. Nesse contexto, nosso primeiro passo foi investigar a expressão e funcionalidade dos receptores P2X por patch clamping. Nossos resultados sugerem a presença de P2X1, de P2X2 e de P2X7. Em seguida, avaliamos por microfluorimetria a funcionalidade dos receptores P2Y, e verificamos com base na ordem de potência a possível presença de P2Y2, de P2Y4, de P2Y6 e de P2Y11. Além disso, confirmamos nossos dados por imunofluorescência. Realizamos também ensaios de migração in vitro e in vivo, para verificar se os nucleotídeos extracelulares poderiam atrair eosinófilos. O ATP foi capaz de induzir a migração dos eosinófilos, enquanto a suramina, um bloqueador P2, aboliu esse efeito, tanto in vitro, utilizando transwell, como in vivo, utilizando um modelo de pleurisia alérgica em ratos. Em seguida, avaliamos o possível papel da panexina-1 como poro associado ao receptor P2X7. Nesse trabalho utilizamos inibidores de hemicanais em experimentos de patch clamp e em ensaios de permeabilização de corante. Os resultados indicam que os inibidores de hemicanais não bloquearam a geração de corrente ou a captação de corante após a ativação do receptor P2X7 em macrófagos de ratos e camundongos. Demonstramos que eosinófilos de rato expressam receptores P2X e P2Y por imunofluorescência. Além disso, demonstramos que a ativação de receptores P2 pode aumentar a migração de eosinófilos in vitro e in vivo. Além disso, foi demonstrado que inibidores de panexina-1 não bloqueiam a captação do corante ou a corrente gerada pela ativação do receptor P2X7. Os nossos resultados demostraram que panexina-1 não é o poro associado ao receptor P2X7 em macrófagos
ATP and other nucleotides are released from cells through regulated pathways or following the loss of plasma membrane integrity. Once outside the cell, these compounds can activate P2 receptors: P2X ionotropic receptors and G protein-coupled P2Y receptors. . Additionally, P2X7 receptor is an important member of the P2X family of ionotropic receptor as its activation opens a non-selective pore allowing the passage of molecules up to 900 Da. Eosinophils represent major effector cells in the allergic inflammatory response and they are, in fact, associated with several physiological and pathological processes. Here we investigate the expression of P2 receptors and roles of those receptors in murine eosinophils. In this context, our first step were to investigate the expression and functionality of the P2X receptors by patch clamping, our results suggest the presence of P2X1, P2X2 and P2X7. Next we evaluate by microfluorimetry the expression of P2Y receptors, our results based in the ranking order of potency suggests the presence of P2Y2, P2Y4, P2Y6 e P2Y11. Moreover, we confirmed our findings by immunofluorescence assays. We also did in vitro and in vivo migration assays to verify whether nucleotides could attract eosinophil. ATP increased migration of eosinophils, while suramin a P2 blocker abolished this effect in both in vitro, using trasnwell, and in vivo, using a model of rat allergic pleurisy. Next, we evaluated the putative role of pannexin-1 as the pore associated to the P2X7 receptor. We used hemichannels inhibitors in patch clamp and dye uptake experiments. The results indicate that they do not interfere with current generation or dye uptake after activation of P2X7R in rat and mouse macrophages. We have demonstrated that rat eosinophils express P2X and P2Y receptors by immunofluorescence. In addition, the activation of P2 receptors can increase migration of eosinophils in vitro and in vivo. Moreover, we demonstrated that specific inhibitors of pannexin-1 did not interfere with the dye uptake or current generated by the P2X7 activation. Our results showed that pannexin-1 is not the pore associated to the P2X7 receptor in macrophages.
Kong, Qiongman. "Regulations and functions of P2Y₂ and P2X₇ nucleotide receptors in the central nervous system." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/4847.
Full textThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on March 19, 2009) Vita. Includes bibliographical references.
Vick, Jonathan. "The Contribution of Purinergic P2X and P2Y Receptors to the Excitability of Mouse Vomeronasal Sensory Neurons." ScholarWorks @ UVM, 2014. http://scholarworks.uvm.edu/graddis/283.
Full textChen, Xiaowei. "Involvement of purinergic P2X and P2Y2 receptors in urinary bladder sensation." Diss., University of Iowa, 2009. https://ir.uiowa.edu/etd/343.
Full textDovlatova, Natalia. "Studies on placelet p2y receptors." Thesis, University of Nottingham, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.517665.
Full textHibell, Amanda Dawn. "Functional characteristics of P2X₇ receptors." Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621665.
Full textZheng, Wenxuan. "Properties of mammalian P2X₇ receptors." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/properties-of-mammalian-p2x7-receptors(1ff23f4a-47eb-4d06-b54c-bd7488c9700c).html.
Full textLiu, Jun. "Structural determinants of P2Y₂ receptor functions." Free to MU campus, others may purchase, 2003. http://wwwlib.umi.com/cr/mo/fullcit?p3100062.
Full textRolf, Michael George. "P2X₁ receptors and human platelet function." Thesis, University of Cambridge, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621241.
Full textGuo, C. "Trafficking and assembly of P2X receptors." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599788.
Full textParamasivam, Anbalakan. "Regulation of immune cell P2X receptors." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612427.
Full textWilkinson, William J. "Structure and function of P2X receptors." Thesis, University of Manchester, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.739404.
Full textJones, Clare Alexa. "Molecular pharmacology of P2X{sub4} and P2X{sub6} receptors for ATP." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620195.
Full textBélanger, Danny. "Heterologous functional interactions of P2X ATP receptors." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=81596.
Full textWildman, Scott Shaw. "Purinergic signalling : sensitisation of recombinant P2X receptors." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325339.
Full textThompson, Kyla Merriom. "Structure/function studies on P2X{sub7} receptors." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620346.
Full textRoyle, Stephen John. "Molecular mechanisms of P2X receptor trafficking." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620612.
Full textMiller, Kerry Jane. "The characterisation of P2X receptor subtypes." Thesis, University of Cambridge, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.624190.
Full textSmith, Fiona Marie. "Molecular determinants of P2X₂ receptor function." Thesis, University of Cambridge, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.624420.
Full textWang, Min. "Role of P2Y₂ nucleotide receptors in reactive astrogliosis." Diss., Columbia, Mo. : University of Missouri-Columbia, 2005. http://hdl.handle.net/10355/4268.
Full textThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file viewed on (January 22, 2007) Includes bibliographical references.
Syed, Nawazish-i.-Husain. "Expression of P2X receptors in rat pulmonary artery." Thesis, University of Strathclyde, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501814.
Full textRoberts, Jonathan A. "Signal transduction of transfected and native P2Y receptors." Thesis, University of Leicester, 1998. http://hdl.handle.net/2381/30614.
Full textBrown, Julia. "Pharmacological evaluation of novel ligands of P2Y receptors." Thesis, University of Wolverhampton, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366088.
Full textChootip, Krongkarn. "P2 receptors in pulmonary vasculature." Thesis, University of Strathclyde, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248554.
Full textHaas, Michael [Verfasser]. "Analysis of functional impairments of the human P2Y 11 nucleotide receptor with the alanine-87 - threonine mutation, and development of novel agonists specific for the human P2Y 11 and P2Y 6 receptors / Michael Haas." Magdeburg : Universitätsbibliothek, 2015. http://d-nb.info/1076590144/34.
Full textDigby, Helen. "Structure/function studies of the P2X receptor." Thesis, University of Leicester, 2007. http://hdl.handle.net/2381/7987.
Full textFarret, Anne. "Effets et mécanismes de l'activation des récepteurs purinergiques P2Y de la cellule beta pancréatique." Thesis, Montpellier 1, 2010. http://www.theses.fr/2010MON1T020/document.
Full textP2Y purinergic receptors play a role in the modulation of insulin secretion and represent a potential therapeutic target for new antidiabetic drugs. In the model of isolated perfused rat pancreas, in functional conditions close to physiology, we have shown that the activation of these receptors amplify the glucose-induced insulin secretion. This effect requires the metabolism of glucose; it is probably related to a rise in intracellular Ca2+ concentration, and is independent from a direct effect on ATP-dependent potassium channels. We have also studied the pancreatic effects of new P2Y receptor agonists, synthesized by the group of Prof. B. Fischer: among these compounds, 2-methylthio-ATP-a-S (A isomer) is a glucose-dependent insulin secretagogue, with high efficacy and potency (EC50 at 28.1 nmol/l), and with very good tissue selectivity. On the other hand, we have investigated the implication of P2Y receptors in cell proliferation, using a model of insulin secreting cell line from rat insulinoma (INS-1E cell line): at the doses used, ATP-a-S (a P2Y receptor agonist) and GLP-1 induce a similar insulin response, but an increase in intracellular cAMP of different magnitude; moreover, in contrast to GLP-1, ATP-a-S is ineffective on cell proliferation. Finally, in collaboration with the group of Prof. C. Gachet, we have shown that the P2Y1 receptor subtype was involved in the insulin response of mice pancreatic islets. Thus, our studies contributed to the improvement of knowledge on P2Y purinergic receptors of pancreatic ß-cells, as regards their mechanisms of action, their effects on insulin secretion and on cell proliferation; we also contributed to the development of specific agonists, potentially interesting for the treatment of type 2 diabetes
Lindsay, Susan L. "P2Y receptors in human sweat glands : localisation and function." Thesis, Glasgow Caledonian University, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404652.
Full textYu, Ningpu. "The role of P2Y₂ nucleotide receptors in vascular inflammation." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/4664.
Full textThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on March 12, 2008) Includes bibliographical references.
Bradley, Helen Joanne. "Characterisation of expression and functional properties of P2Xz receptors." Thesis, University of Leeds, 2010. http://etheses.whiterose.ac.uk/21134/.
Full textMenzies, Robert Ian. "Susceptibility to hypertensive renal injury mediated by P2X receptors." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/14191.
Full textAhn, Jae Suk. "Regulation of P2Y₂ nucleotide receptor expression in salivary glands." free to MU campus, to others for purchase, 2001. http://wwwlib.umi.com/cr/mo/fullcit?p3012944.
Full textLiao, Zhongji. "The role of the P2Y₂ nucleotide receptor in inflammation the mechanisms of P2Y₂ receptor-mediated activation of G proteins /." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://etd.missouri.edu/Fall2007/Dissertation/LiaoZ-030509-D8457/.
Full textThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on March 10, 2009) Includes bibliographical references.
Reschke, Cristina Ruedell. "RECEPTORES EP1 E EP3 MODULAM AS CRISES EPILÉPTICAS INDUZIDAS POR PENTILENOTETRAZOL E ÁCIDO CAÍNICO EM CAMUNDONGOS." Universidade Federal de Santa Maria, 2013. http://repositorio.ufsm.br/handle/1/3852.
Full textEpilepsy is one of the most common neurologic disorders. It has been suggested that seizures may be facilitaded by inflammation. PGE2 is one of the most important inflammatory mediators, and facilitates pentylenetetrazol (PTZ)-induced seizures by stimulating EP1 and EP3 receptors. However, up to the present moment, no study has investigated whether EP1 and EP3 receptors blocking attenuate seizures induced by convulsants other than PTZ. It is also unknown whether Na+,K+-ATPase activity alterations are involved in such an effect. Therefore, in the current study we investigated whether EP1 and EP3 ligands (agonists and antagonists) modulate PTZ- and kainic acid (KA)-induced seizures, and whether alterations in Na+,K+-ATPase activity mediate such a protective effect, in mice. EP1 and EP3 antagonists (ONO-8713 and ONO-AE3-240, respectively, 10 Og/kg, s.c.) attenuated PTZ (60 mg/kg, i.p.)- and KA (20 mg/kg, i.p.)-induced seizures. The respective agonists (ONO-DI-004 and ONO-AE-248, 10 Og/kg, s.c.) facilitated seizures in both acute models, and at noneffective doses, prevented the protective effects of the antagonists. Animals injected with PTZ presented decreased Na+,K+-ATPase activity in the cerebral cortex and hippocampus. On the other hand, animals injected with KA presented increased Na+,K+-ATPase activity in the same cerebral structures at the end of the experiment. These divergent findings suggest that alterations in Na+,K+-ATPase activity in both acute models depends on the convulsant agent used and make difficult to establish a relationship between Na+,K+-ATPase activity and seizure development. Moreover, EP1 and EP3 antagonists administration abolished Na+,K+- ATPase activity alterations induced by PTZ and KA, in such a way that these alterations seem to be related more to the presence of ictal phenomenon itself than to the seizure induction mechanisms. Notwithstanding, the currrent results clearly show that EP1 and EP3 receptors might constitute novel targets for anticonvulsants development, since EP1 and EP3 decreased seizures, regardless of the convulsant agent used.
A epilepsia é uma das disfunções neurológicas mais comuns. Tem sido sugerido que as crises epilépticas podem ser facilitadas pela ocorrência de inflamação. A PGE2 é um dos mediadores inflamatórios mais importantes que, agindo por meio dos receptores EP1 e EP3, facilita as convulsões induzidas por pentilenotetrazol (PTZ). Contudo, até a presente data, nenhum estudo investigou, de maneira sistêmica, se a ativação ou bloqueio de receptores EP1 e EP3 facilitam as convulsões induzidas por outros agentes; tampouco se alterações na atividade da Na+,K+-ATPase estão envolvidas nesse efeito. Assim, no presente estudo, investigamos se ligantes (agonistas e antagonistas) de receptores EP1 e EP3 modificam as crises induzidas por PTZ e ácido caínico (KA), e se tais efeitos estão associados a alterações na atividade da enzima Na+,K+-ATPase, em camundongos. Os antagonistas EP1 e EP3 (ONO-8713 e ONO-AE3-240, respectivamente, 10 Og/Kg, s.c.) atenuaram as convulsões induzidas por PTZ (60 mg/Kg, i.p.) e KA (20 mg/Kg). Os seus respectivos agonistas (ONO-DI-004 e ONO-AE-248 de 10 Og/Kg, s.c.) facilitaram as convulsões em ambos modelos agudos de crises epilépticas e, em doses não efetivas para gerar crises, preveniram os efeitos dos antagonistas. Os animais submetidos à administração de PTZ apresentaram, ao final do experimento, a atividade Na+,K+-ATPásica diminuída no córtex cerebral e hipocampo. Por outro lado, animais tratados com KA apresentaram um aumento na atividade Na+,K+-ATPásica nestas mesmas estruturas, que se correlacionou positivamente com a vigência de status epilepticus no momento do sacrifício. Os achados divergentes no que diz respeito à alteração da atividade da Na+,K+-ATPase nos dois modelos de crises agudas sugere que tais alterações estejam relacionadas ao tipo de agente convulsivante utilizado, e dificultam estabelecer, de forma inequívoca, uma relação entre atividade desta ATPase e sensibilidade à crises agudas. Ademais, a administração de antagonistas EP1 e EP3 aboliu as alterações da atividade da Na+,K+-ATPase induzidas tanto por PTZ como por KA, de tal forma que estas parecem estar mais associadas com o fenômeno ictal em si, do que com os mecanismos de indução da crise. Contudo, os resultados mostram de forma clara que os receptores EP1 e EP3 podem se constituir possíveis novos alvos para o desenvolvimento de drogas antiepilépticas, pois antagonistas EP1 e EP3 diminuíram as crises, independente do agente convulsivante utilizado.
Zambon, Alexander Carlos. "Cloning and signaling properties of canine P2Y₂ and P2Y₁₁ receptors : implications for epithelial cell signaling /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2000. http://wwwlib.umi.com/cr/ucsd/fullcit?p9974757.
Full textMajumder, Paromita. "Análise dos receptores P2X2 e P2X4 durante a diferenciação neuronal." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-05102007-145008/.
Full textDuring the development of the nervous system, oscillations of intracellular calcium concentrations activate programs of gene expression resulting in proliferation, migration and neuronal differentiation of embryonic cells. In this thesis, the participation of ionotropic P2X2 and P2X4 receptor subtypes, whose receptor channels are highly permeable for calcium influx in the cells, was studied during the process of neuronal differentiation. We have identified differential gene expression of purinergic receptors in undifferentiated and neuronal-differentiated P19 cells. P2X4 receptor expression was present along neuronal differentiation of P19 cells, whereas P2X2 receptor expression was only detected when P19 cells became neurons. Based on purinergic receptor pharmacology we have determined the participation of P2X4 receptors in addition to metabotropic P2Y2 receptors in the formation of embryonic bodies as prerequisites for phenotype determination of P19 neural progenitor cells. Final neuronal maturation of P19 cells in the presence or absence of agonists or antagonists of purinergic receptors implicated the involvement of P2X2, P2Y1, and P2Y2 in the determination of the final neuronal phenotype, such as expression of NMDA-glutamate and cholinergic receptors. In order to further evaluate the functions of these P2X receptors and due to the absence of specific inhibitors for these receptor subtypes, we have used the SELEX technique (Systematic Evolution of Ligands by EXponential enrichment) to select for specific inhibitors for P2X2 and P2X4 receptors. The 2\' -F-pyrimidine modified, nuclease- resistant combinatorial SELEX RNA pool enriched with inhibitors of P2X4 receptors following nine cycles of in vitro selection (cycle 9-P2X4) specifically interacted with P2X4 receptors and not with P2X2 or P2X7 receptors as verified in radioligand-receptor binding studies. Moreover, whole-cell recording measurements using astrocytoma cells expressing recombinant rat P2X2 or P2X4 receptors showed inhibition of P2X4 but not of P2X2 receptors by the selected RNA molecules. RNA molecules selected in vitro in 11 reiterative SELEX cycles using the P2X2 receptor as target specifically bound to membrane extracts containing recombinant P2X2 receptors. From both selected RNA libraries (against P2X4 and P2X2 receptors) aptamers, as RNA molecules with identified sequences and high-affinity binding, were identified by cloning and DNA sequencing. The presence of these aptamers in whole-cell recording experiments resulted in 30-80% inhibition of ATP-induced receptor activity and did not provoke any inhibitory effects on P2X receptors which had not been used as selection target. The activity of the aptamers selected using recombinant receptors as targets in inhibiting wild-type P2X4 or P2X2 receptors was verified in whole-cell recording experiments with PC12 cells which endogenously express both receptor subtypes. In addition of having developed aptamers as tools to elucidate P2X2 and P2X4 receptor functions during neuronal differentiation, these nuclease-resistant aptamers are suitable for in vivo use and may turn into therapeutics in the inhibition of purinergic receptor participation in pathophysiological conditions.
Bernier, Louis-Philippe. "Functional regulation of P2X receptor channels by phosphoinositides." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110361.
Full textLongtemps après la découverte de sa présence dans l'ADN et de son rôle en tant que principale source d'énergie chimique dans la cellule, le nucléotide adenosine-5'-triphosphate (ATP) est maintenant considéré comme une importante molécule de signalisation extracellulaire. La transmission purinergique est activement impliquée dans plusieurs processus physiologiques, notamment dans la neuro- et glio-transmission, la modulation de la réponse immunitaire innée et adaptative, la constriction vasculaire et la coagulation sanguine. Elle participe aussi à la génération et au maintien de divers états pathologiques, tels la douleur chronique neuropathique et inflammatoire.La signalisation purinergique est impliquée dans des processus aussi diversifiés par l'entremise d'une seule molécule de signalisation grâce à une grande variété de récepteurs activés par l'ATP. Les deux principaux types de récepteurs sensibles à l'ATP sont les récepteurs ionotropiques P2X et les récepteurs métabotropiques P2Y. La famille P2X de canaux ioniques activés par l'ATP est composée de sept sous-unités qui s'assemblent comme trimères pour former des récepteurs possédant divers profils fonctionnels et pharmacologiques. Comme tous les canaux ioniques, l'activité des P2X est étroitement régulée par des mécanismes de régulation orthostériques et allostériques. Cette thèse démontre l'existence d'un nouveau type de mécanisme de régulation post-traductionnel, où les niveaux de phosphoinositides (PIPn) intracellulaires modulent l'activité de canal ionique des récepteurs P2X.Le premier article porte sur le sous-type P2X1, qui contribue à la contraction des muscles lisses dans les vaisseaux sanguins et le canal déférent, ainsi qu'à l'agrégation plaquettaire. Nous démontrons que l'activité du récepteur canal P2X1 est positivement régulée par les PI(4,5)P2 (PIP2) membranaires. La déplétion des niveaux intracellulaires de PIP2 diminue l'amplitude du courant ionique induit par P2X1. Nous montrons que le couplage direct entre le domaine C-terminal cytosolique de P2X1 et PIP2 est nécéssaire pour l'expression complète de l'activité de P2X1.Le second article de cette thèse décrit la régulation PIPn-dépendante du récepteur canal P2X4, qui joue un rôle majeur dans la génération et le maintien de la douleur neuropathique et inflammatoire par son expression dans les microglies de la moelle épinière. Nous démontrons que le fonctionnement de P2X4 dépend des niveaux de PIP2 et de PI(3,4,5)P3 (PIP3). Les deux types de phospholipides potentialisent le courant ionique ainsi que l'entrée de calcium par le canal P2X4 en se liant directement au domaine C-terminal des sous-unités P2X4. Dans le troisième rapport, nous étudions les caractéristiques moléculaires de l'interaction entre les PIPn membranaires et les récepteurs P2X directement modulés par ces phospholipides. En analysant les effets fonctionnels de diverses mutations effectuées sur le domaine C-terminal des sous-types PIPn-dépendant P2X1, P2X4 et P2X7 et sur le sous-type PIPn-indépendant P2X5, nous identifions le motif nécessaire à la liaison P2X-PIPn et à la régulation fonctionnelle du canal par les PIPn.Le dernier article de cette thèse examine les changements dynamiques de la perméabilité du canal ionique apportés par une activation soutenue des récepteurs microgliaux P2X4. Nous montrons que, lors d'une application soutenue d'ATP, les canaux P2X4 forment des pores à haute conductance permettant le flux de molécules organiques à haut poids moléculaire. La formation de larges pores par les récepteurs P2X7 a été étudiée intensivement; nous démontrons ici que la perméation induite par P2X4 est mécanistiquement distincte et, à l'opposé de P2X7, ne mène à aucun réarrangement de la structure membranaire ni à la mort cellulaire. Les PIPn membranaires potentialisent la formation de ces pores à haute conductance par P2X4, suggérant que cette propriété peut être régulée par des changements intracellulaires des niveaux de PIPn.
Francis, Joanna. "Interactions of PDZ proteins with kainate receptor subunits." Thesis, University of Bristol, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274761.
Full textGoodey, G. C. "P2X receptor function in an extreme ionic environment." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1399846/.
Full textWhite, Pamela J. "The role of P2Y receptors in human vascular smooth muscle." Thesis, De Montfort University, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413773.
Full textMoore, Samantha. "The role of fast ATP-Gated P2X receptors in inflammation." Thesis, University of Bath, 2008. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.512309.
Full textJiang, Ruotian. "Molecular modus operandi of ligand-gated ion channels : Studies of trimeric P2X receptors and pentameric GABA A receptors." Strasbourg, 2011. http://www.theses.fr/2011STRA6086.
Full textThis thesis, by using various chemical and biological tools, focuses on the molecular modus operandi of two different superfamilies of ligand-gated ion channels: P2XRs and GABAARs. P2XR is a cation-selective ion channel gated by extracellular ATP (and is implicated in diverse physiological processes, from synaptic transmission to inflammation to the sensing of taste and pain. Here I studied the molecular mechanism underlying ATP binding and channel opening of the P2X receptors. In the ATP-binding site study, we definitely localized the ATP-binding sites in P2X2 receptor through affnity labeling. Our results thus define a large and dynamic inter-subunit ATP-binding pocket. In the “gating”†part, an inter-subunit salt bridge located at the “body” domain that regulates channel gating movement was identified by using charge reversal and charge swapping combined with double mutant cycle analysisPentameric GABAARs form chloride permeable ion channels and mediate inhibitory synaptic transmission in the central nervous system. The modulation of their action is critical for brain normal function and for various pathophysiological conditions. In the GABAARs part, using patch-clamp electrophysiology, we described the allosteric modulation of GABAARs by a series of synthetic compounds that are trans-retrochalcones belonging to the flavonoids family. We characterized their subunit-dependent positive modulations at both synaptic and extrasynaptic GABAARs. Our data reveal an original mode of action and provide a rational basis for hypothesis-driven drug discovery efforts with emphasis on the retrochalcone scaffold for treating GABAA-related central nervous system disorders
Webb, Rachel J. "Characterisation of P2-receptors on human platelets." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342989.
Full textLindner, Anna. "Untersuchung der Interaktion der Untereinheiten im humanen P2X2- und P2X2/3-Rezeptor durch Cystein-substituierte Aminosäuren." Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-189913.
Full textTengah, Ampuan Haji Mohamad Asrin Ampuan Haji. "P2Y receptor-mediated excitation-contraction coupling in pulmonary arteries." Thesis, University of Strathclyde, 2010. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=14353.
Full textAndrew-Adiamah, Jemma. "The P2X receptor mediated regulation of inhibitory synaptic transmission." Thesis, University of Warwick, 2012. http://wrap.warwick.ac.uk/59614/.
Full textDayl, Sudad Amer. "Molecular modelling of ATP-gated P2X receptor ion channels." Thesis, University of Leicester, 2018. http://hdl.handle.net/2381/42761.
Full textPappas, Beverly. "Mechanistic Study of p23-Mediated Aryl Hydrocarbon Receptor Expression." Scholarly Commons, 2018. https://scholarlycommons.pacific.edu/uop_etds/3131.
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