Creatina aumenta a atividade da Na+,K+-ATPase e previne o aparecimento das convulsões induzidas por pentilenotetrazol em ratos
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/8946 |
Resumo: | Creatine, an endogenous guanidino compound produced on liver, kidneys, pancreas, testes and brain, has been aim of several studies over the last years. Although most studies attribute the effects of creatine to their energetic buffer role, recent findings have suggested actions non-related to energy metabolism. Researches have shown that this compound may act as a neuromodulator in the central nervous system (CNS). Among these neuromodulatory actions, was demonstrated that creatine modulates NMDA receptors in rat hippocampal slices. It is well know that stimulation of these receptors activates Na+,K+-ATPase. Moreover, little is known about the acute role of this compound on CNS. Thus, the objective of the chapter I of this paper was to investigate the effect of creatine on Na+,K+-ATPase activity and the intracellular signaling pathway involved. The results showed that creatine treatment of rat hippocampal slices increased Na+,K+-ATPase α2/3 activity in vitro. The intracerebroventricular administration of this compound also increased the enzyme activity, ex vivo. Furthermore, creatinine and phosphocreatine treatment of hippocampal slices did not alter the enzyme activity, suggesting that the creatine mechanism of action is independent of energy metabolism. Additionally, we showed the involvement of NMDA-NR2B and calcineurin. We found also the involvement of the PKA and PKC in the effect of creatine on Na+,K+-ATPase activity. In the second chapter of this study, we decide to verify the effect of acute creatine administration on PTZ-induced seizures, since this convulsant agent inhibits Na+,K+-ATPase activity without alter bioenergetic cellular state. We found that creatine treatment protected against behavioral and electroencephalographic seizures induced by PTZ. Moreover, creatine acute treatment prevented PTZ-induced inhibition of Na+,K+-ATPase activity. Based on present findings, we suggest that creatine may act through an alternative mechanism, independent of energetic metabolism, by modulation of Na+,K+-ATPase activity. |
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2010-05-112010-05-112010-02-26RAMBO, Leonardo Magno. CREATINE INCREASES Na+,K+-ATPase ACTIVITY AND PREVENTS SEIZURES INDUCED BY PENTYLENETETRAZOLE IN RATS. 2010. 108 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2010.http://repositorio.ufsm.br/handle/1/8946Creatine, an endogenous guanidino compound produced on liver, kidneys, pancreas, testes and brain, has been aim of several studies over the last years. Although most studies attribute the effects of creatine to their energetic buffer role, recent findings have suggested actions non-related to energy metabolism. Researches have shown that this compound may act as a neuromodulator in the central nervous system (CNS). Among these neuromodulatory actions, was demonstrated that creatine modulates NMDA receptors in rat hippocampal slices. It is well know that stimulation of these receptors activates Na+,K+-ATPase. Moreover, little is known about the acute role of this compound on CNS. Thus, the objective of the chapter I of this paper was to investigate the effect of creatine on Na+,K+-ATPase activity and the intracellular signaling pathway involved. The results showed that creatine treatment of rat hippocampal slices increased Na+,K+-ATPase α2/3 activity in vitro. The intracerebroventricular administration of this compound also increased the enzyme activity, ex vivo. Furthermore, creatinine and phosphocreatine treatment of hippocampal slices did not alter the enzyme activity, suggesting that the creatine mechanism of action is independent of energy metabolism. Additionally, we showed the involvement of NMDA-NR2B and calcineurin. We found also the involvement of the PKA and PKC in the effect of creatine on Na+,K+-ATPase activity. In the second chapter of this study, we decide to verify the effect of acute creatine administration on PTZ-induced seizures, since this convulsant agent inhibits Na+,K+-ATPase activity without alter bioenergetic cellular state. We found that creatine treatment protected against behavioral and electroencephalographic seizures induced by PTZ. Moreover, creatine acute treatment prevented PTZ-induced inhibition of Na+,K+-ATPase activity. Based on present findings, we suggest that creatine may act through an alternative mechanism, independent of energetic metabolism, by modulation of Na+,K+-ATPase activity.A creatina, um composto guanidínico endógeno, sintetizado pelos rins, fígado, pâncreas, testículos e cérebro, tem sido alvo de diversos estudos ao longo dos últimos anos. Apesar da grande maioria dos estudos atribuírem os efeitos da creatina ao seu papel de tamponamento de energia, recentes achados têm proposto ações não relacionadas ao metabolismo energético. Estudos têm demonstrado que este composto pode agir como neuromodulador no Sistema Nervoso Central (SNC). Dentre estas ações neuromodulatórias, demonstrou-se que a creatina pode modular os receptores do subtipo N-metil- D-aspartato (NMDA) em fatias de hipocampo de ratos. É bem descrito na literatura que a estimulação destes receptores ativa a enzima Na+,K+-ATPase. Além disso, pouco se sabe sobre o papel agudo deste composto no SNC. Desta forma, o objetivo do capítulo I deste estudo foi verificar o efeito da creatina sobre a atividade da enzima Na+,K+-ATPase, bem como sua provável via de sinalização intracelular. Os resultados demonstraram que a incubação de fatias de hipocampo de ratos, com creatina, aumentou a atividade da enzima Na+,K+-ATPase α2/3 in vitro e, que a injeção intracerebroventrical (i.c.v) deste composto, aumentou a atividade da enzima ex vivo. Verificou-se também que o tratamento das fatias hipocampais com fosfocreatina e creatinina não alterou a atividade enzimática, sugerindo que o mecanismo de ação da creatina é independente do metabolismo energético. Além disso, foi evidenciada a participação dos receptores NMDA-NR2B, bem como a ativação da enzima calcineurina. Nós constatamos também o envolvimento das enzimas proteína quinase dependente de AMPc (PKA) e da proteína quinase C (PKC) no efeito da creatina sobre a atividade da enzima Na+,K+-ATPase. No segundo capítulo deste estudo, decidimos verificar o efeito da administração aguda de creatina sobre as convulsões induzidas por pentilenotetrazol (PTZ), uma vez que este agente quimioconvulsivante inibe a enzima Na+,K+-ATPase sem alterar o status bioenergético celular. Constatamos que a creatina protegeu contra as convulsões comportamentais e eletroencefalográficas induzidas por PTZ. Além disso, o tratamento agudo com creatina preveniu a inibição da atividade da enzima Na+,K+-ATPase induzida por PTZ. Com base nestas evidências, sugerimos que este composto guanidínico pode estar atuando através de um mecanismo alternativo, não dependente do metabolismo energético, através da modulação da atividade da enzima Na+,K+-ATPase.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em FarmacologiaUFSMBRFarmacologiaCreatinaNa+K+-ATPasePTZNMDACreatineNa+K+-ATPasePTZNMDACNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIACreatina aumenta a atividade da Na+,K+-ATPase e previne o aparecimento das convulsões induzidas por pentilenotetrazol em ratosCreatine increases Na+,K+-ATPase activity and prevents seizures induced by pentylenetetrazole in ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisRoyes, Luiz Fernando Freirehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705849Y0Rubin, Maribel Antonellohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794806H7Schetinger, Maria Rosa Chitolinahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4219902U6Rambo, Leonardo Magno201000000000400500500500500c83ec235-e54e-44ae-bea7-573d588ca1830ce8a699-93e4-49d8-9d86-3bb5ceb7afd854e815ae-8af3-4abc-8a86-fc8ea077520b93acb9e6-39fa-412c-84a4-a90a4863b53einfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALRAMBO, LEONARDO MAGNO.pdfapplication/pdf1960064http://repositorio.ufsm.br/bitstream/1/8946/1/RAMBO%2c%20LEONARDO%20MAGNO.pdf51e382bcc4c09924e2dc107c9f3a8019MD51TEXTRAMBO, LEONARDO MAGNO.pdf.txtRAMBO, LEONARDO MAGNO.pdf.txtExtracted texttext/plain170435http://repositorio.ufsm.br/bitstream/1/8946/2/RAMBO%2c%20LEONARDO%20MAGNO.pdf.txt66ed8e61309acb1f328d90581d35e550MD52THUMBNAILRAMBO, LEONARDO MAGNO.pdf.jpgRAMBO, LEONARDO MAGNO.pdf.jpgIM Thumbnailimage/jpeg5810http://repositorio.ufsm.br/bitstream/1/8946/3/RAMBO%2c%20LEONARDO%20MAGNO.pdf.jpg3bfa626d575c65cabe5867064e3f70efMD531/89462022-02-21 14:48:59.071oai:repositorio.ufsm.br:1/8946Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-02-21T17:48:59Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Creatina aumenta a atividade da Na+,K+-ATPase e previne o aparecimento das convulsões induzidas por pentilenotetrazol em ratos |
dc.title.alternative.eng.fl_str_mv |
Creatine increases Na+,K+-ATPase activity and prevents seizures induced by pentylenetetrazole in rats |
title |
Creatina aumenta a atividade da Na+,K+-ATPase e previne o aparecimento das convulsões induzidas por pentilenotetrazol em ratos |
spellingShingle |
Creatina aumenta a atividade da Na+,K+-ATPase e previne o aparecimento das convulsões induzidas por pentilenotetrazol em ratos Rambo, Leonardo Magno Creatina Na+ K+-ATPase PTZ NMDA Creatine Na+ K+-ATPase PTZ NMDA CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Creatina aumenta a atividade da Na+,K+-ATPase e previne o aparecimento das convulsões induzidas por pentilenotetrazol em ratos |
title_full |
Creatina aumenta a atividade da Na+,K+-ATPase e previne o aparecimento das convulsões induzidas por pentilenotetrazol em ratos |
title_fullStr |
Creatina aumenta a atividade da Na+,K+-ATPase e previne o aparecimento das convulsões induzidas por pentilenotetrazol em ratos |
title_full_unstemmed |
Creatina aumenta a atividade da Na+,K+-ATPase e previne o aparecimento das convulsões induzidas por pentilenotetrazol em ratos |
title_sort |
Creatina aumenta a atividade da Na+,K+-ATPase e previne o aparecimento das convulsões induzidas por pentilenotetrazol em ratos |
author |
Rambo, Leonardo Magno |
author_facet |
Rambo, Leonardo Magno |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Royes, Luiz Fernando Freire |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705849Y0 |
dc.contributor.referee1.fl_str_mv |
Rubin, Maribel Antonello |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794806H7 |
dc.contributor.referee2.fl_str_mv |
Schetinger, Maria Rosa Chitolina |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4219902U6 |
dc.contributor.author.fl_str_mv |
Rambo, Leonardo Magno |
contributor_str_mv |
Royes, Luiz Fernando Freire Rubin, Maribel Antonello Schetinger, Maria Rosa Chitolina |
dc.subject.por.fl_str_mv |
Creatina Na+ K+-ATPase PTZ NMDA |
topic |
Creatina Na+ K+-ATPase PTZ NMDA Creatine Na+ K+-ATPase PTZ NMDA CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Creatine Na+ K+-ATPase PTZ NMDA |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Creatine, an endogenous guanidino compound produced on liver, kidneys, pancreas, testes and brain, has been aim of several studies over the last years. Although most studies attribute the effects of creatine to their energetic buffer role, recent findings have suggested actions non-related to energy metabolism. Researches have shown that this compound may act as a neuromodulator in the central nervous system (CNS). Among these neuromodulatory actions, was demonstrated that creatine modulates NMDA receptors in rat hippocampal slices. It is well know that stimulation of these receptors activates Na+,K+-ATPase. Moreover, little is known about the acute role of this compound on CNS. Thus, the objective of the chapter I of this paper was to investigate the effect of creatine on Na+,K+-ATPase activity and the intracellular signaling pathway involved. The results showed that creatine treatment of rat hippocampal slices increased Na+,K+-ATPase α2/3 activity in vitro. The intracerebroventricular administration of this compound also increased the enzyme activity, ex vivo. Furthermore, creatinine and phosphocreatine treatment of hippocampal slices did not alter the enzyme activity, suggesting that the creatine mechanism of action is independent of energy metabolism. Additionally, we showed the involvement of NMDA-NR2B and calcineurin. We found also the involvement of the PKA and PKC in the effect of creatine on Na+,K+-ATPase activity. In the second chapter of this study, we decide to verify the effect of acute creatine administration on PTZ-induced seizures, since this convulsant agent inhibits Na+,K+-ATPase activity without alter bioenergetic cellular state. We found that creatine treatment protected against behavioral and electroencephalographic seizures induced by PTZ. Moreover, creatine acute treatment prevented PTZ-induced inhibition of Na+,K+-ATPase activity. Based on present findings, we suggest that creatine may act through an alternative mechanism, independent of energetic metabolism, by modulation of Na+,K+-ATPase activity. |
publishDate |
2010 |
dc.date.accessioned.fl_str_mv |
2010-05-11 |
dc.date.available.fl_str_mv |
2010-05-11 |
dc.date.issued.fl_str_mv |
2010-02-26 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
RAMBO, Leonardo Magno. CREATINE INCREASES Na+,K+-ATPase ACTIVITY AND PREVENTS SEIZURES INDUCED BY PENTYLENETETRAZOLE IN RATS. 2010. 108 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2010. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/8946 |
identifier_str_mv |
RAMBO, Leonardo Magno. CREATINE INCREASES Na+,K+-ATPase ACTIVITY AND PREVENTS SEIZURES INDUCED BY PENTYLENETETRAZOLE IN RATS. 2010. 108 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2010. |
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http://repositorio.ufsm.br/handle/1/8946 |
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UFSM |
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Farmacologia |
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Universidade Federal de Santa Maria |
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