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Análise do transporte de glutamato e GABA em epimastigotas de Trypanosoma cruzi.; Analysis of glutamate and GABA Transport in Trypanosoma Cruzi.

Rojas, Robert Leonardo Galvez
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 09/08/2007 PT
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37.08%
A importância de aminoácidos em tripanossomatídeos vai além da síntese de aminoácidos, envolvendo processos tais como a diferenciação, osmorregulação e metabolismo energético. A disponibilidade dos aminoácidos envolvidos nestas funções depende, entre outras coisas, de seu transporte na célula. Aqui, caracterizamos o transporte de glutamato e GABA do parasita protozoário humano Trypanosoma cruzi. No transporte de glutamato dados cinéticos amostram um único sistema saturável com uma Km de 0.30 mM e uma velocidade máxima de 98.34 pmoles min-1 per 2 x 107 células para epimastigotas é 20 pmoles min-1 per 2 x 107 células para trypomastigotas, e uma Vmax de 84.45 pmoles/min/20x106 células com uma Km de 0.4 mM para o sistema de transporte de GABA. O transporte não apresentou alterações em condições de jejum de até 3 horas. Aspartato, alanina, glutamina, asparagina, metionina, oxaloacetato é alfa-cetoglutarato competiram com o substrato em concentrações dez vezes em excesso na incorporação de glutamato. Interessantemente, o transporte de glutamato aumentou fortemente na presença de GABA. O transporte de glutamato foi fortemente dependente do pH, mas não de concentrações de Na+ e K+ no meio extracelular...

Liberação de 3H-GABA por tecido estriatal de ratos: caracterização e efeitos da lesão experimental parkinsoniana; Rat striatal tissue 3H-GABA release: Characterization and effects of experimental parkinsonian injury

Homem, Karen Silvia de Carvalho
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 27/06/2013 PT
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37.05%
A Doença de Parkinson, uma condição neurodegenerativa e progressiva, está relacionada à morte de neurônios localizados na Substância Negra compacta, um dos componentes dos Núcleos da Base. Quando há a morte de neurônios dopaminérgicos nigrais, esta via modulatória é perdida, levando ao desequilíbrio entre as vias direta e indireta, esta última tendo sua atividade aumentada em detrimento da outra. O estriado tem um papel importante no recebimento e filtração de sinais motores corticais e talâmicos e suas maiores populações neuronais são GABAérgicas, demonstrando a importância do neurotransmissor GABA nesta modulação. O estriado recebe projeções dopaminérgicas vindas da Substância Negra compacta e, na falta desta aferentação, surgem os sintomas e sinais da Doença de Parkinson. Nosso objetivo é caracterizar a liberação de GABA nesta estrutura, avaliando os efeitos de outros transmissores e também o papel de alguns sinalizadores intracelulares neste processo. Para isto, empregamos o método de superfusão e liberação de GABA radiomarcado, previamente carregado, em tecido picado in vitro. A lesão nigral é produzida por cirurgia estereotáxica e microinjeção de 6-OHDA no feixe medial prosencefálico (mfb). Diversas drogas foram utilizadas para avaliarmos diferentes passos na liberação do transmissor. Concluímos que a liberação é fortemente dependente de cálcio e segue o modelo de exocitose vesicular...

Aluminium-induced impairment of Ca2+ modulatory action on GABA transport in brain cortex nerve terminals

Cordeiro, J. M.; Silva, V. S.; Oliveira, C. R.; Goncalves, P. P.
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
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The gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in vertebrate CNS. At GABAergic synapses, a high-affinity transporter exists, which is responsible for GABA reuptake and release during nemotransmission. GABA transporter activity depends on the phosphorylation/dephosphorylation state, being modulated by Ca2+/calmodulin-dependent protein phosphatase 2B (calcineurin). Aluminium is known to interfere with the Ca2+ /calmodulin signalling pathway. In this work, we investigate the action of aluminium, on GABA translocation mediated by the high-affinity transporter, using synaptic plasma membrane (SPM) vesicles and synaptosomes isolated from brain cortex. Aluminium completely relieved Ca2+ downregulation of GABA transporter, when mediating uptake or release. Accordingly, aluminium inhibited Ca2+ /calmodulin-dependent calcineurin activity present in SPM, in a concentration-dependent manner. The deleterious action of aluminium on the modulation of GABA transport was ascertained by comparative analysis of the aluminium effect on GABA uptake and release, under conditions favouring SPM dephosphorylation (presence of intracellular micromolar Ca2+) or phosphorylation (absence of Ca2+ and/or presence of W-7, a selective calmodulin antagonist). In conclusion...

Production of gaba (γ - aminobutyric acid) by microorganisms: a review

Dhakal,Radhika; Bajpai,Vivek K.; Baek,Kwang-Hyun
Fonte: Sociedade Brasileira de Microbiologia Publicador: Sociedade Brasileira de Microbiologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2012 EN
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37.1%
GABA (γ-aminobutyric acid) is a four carbon non-protein amino acid that is widely distributed in plants, animals and microorganisms. As a metabolic product of plants and microorganisms produced by the decarboxylation of glutamic acid, GABA functions as an inhibitory neurotransmitter in the brain that directly affects the personality and the stress management. A wide range of traditional foods produced by microbial fermentation contain GABA, in which GABA is safe and eco-friendly, and also has the possibility of providing new health-benefited products enriched with GABA. Synthesis of GABA is catalyzed by glutamate decarboxylase, therefore, the optimal fermentation condition is mainly based on the biochemical properties of the enzyme. Major GABA producing microorganisms are lactic acid bacteria (LAB), which make food spoilage pathogens unable to grow and act as probiotics in the gastrointestinal tract. The major factors affecting the production of GABA by microbial fermentation are temperature, pH, fermentation time and different media additives, therefore, these factors are summarized to provide the most up-dated information for effective GABA synthesis. There has been a huge accumulation of knowledge on GABA application for human health accompanying with a demand on natural GABA supply. Only the GABA production by microorganisms can fulfill the demand with GABA-enriched health beneficial foods.

GABA and glutamate transporters: new events and function in the vertebrate retina

Nascimento,José Luiz Martins do; Sawada,Luis Armando; Oliveira,Karen Renata Matos; Crespo-López,Maria Elena; Silva,Anderson Manoel Herculano Oliveira da; Hamoy,Moisés; Silva,Consuelo Yumiko Yoshioka e; Bastos,Gilmara Nazareth Tavares; Soeiro-Pantoja,We
Fonte: Pontificia Universidade Católica do Rio de Janeiro; Universidade de Brasília; Universidade de São Paulo Publicador: Pontificia Universidade Católica do Rio de Janeiro; Universidade de Brasília; Universidade de São Paulo
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2013 EN
Relevância na Pesquisa
37.05%
The neural retina is a highly complex tissue composed of excitatory and inhibitory neurons and glial cells. Glutamate, the main excitatory neurotransmitter, mediates information transfer from photoreceptors, bipolar cells, and ganglion cells, whereas interneurons, mainly amacrine and horizontal cells, use γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter. In this review we place an emphasis on glutamate and GABA transporters as highly regulated molecules that play fundamental roles in neurotransmitter clearance, neurotransmitter release, and oxidative stress. We pharmacologically characterized glutamate transporters in chicken retina cells and identified two glutamate transporters: one Na+-dependent transporter and one Na+-independent transporter. The Na+-dependent uptake system presented characteristics related to the high-affinity xAG- system (EAAT1), and the Na+-independent uptake system presented characteristics related to the xCG- system, which highly contributes to glutamate transport in the retina. Glutamate shares the xCG- system with another amino acid, L-cysteine, suggesting the possible involvement of glutathione. Both transporter proteins are present mainly in Müller glial cells. GABA transporters (GATs) mediate high-affinity GABA uptake from the extracellular space and terminate the synaptic action of GABA in the central nervous system. GABA transporters can be modulated by molecules that act on specific sites to promote transporter phosphorylation and dephosphorylation. In addition to a role in the clearance of GABA...

Efeito modulador da glutationa na libera??o de gaba induzida por glutamato em retinas de embri?o de galinha

PEREIRA, Tiago de Lima
Fonte: Universidade Federal do Pará Publicador: Universidade Federal do Pará
Tipo: Dissertação de Mestrado
POR
Relevância na Pesquisa
37.16%
O ?cido ?-aminobut?rico (GABA) e o glutamato s?o, respectivamente, os principais neurotransmissores inibit?rio e excitat?rio no Sistema Nervoso Central (SNC) e s?o fundamentais para o processamento visual. Estudos revelam que o glutamato induz libera??o de GABA na retina. Trabalhos pr?vios tamb?m apontam que compostos ti?is regulam a libera??o de GABA, mas ainda n?o s?o totalmente esclarecidos os efeitos de ti?is (-SH) sobre os n?veis end?genos deste neurotransmissor na retina. Neste interm?dio, a glutationa (GSH) al?m de ser o mais importante dos compostos ti?is, vem demonstrando exercer um papel neuromodulador na libera??o de neurotransmissores. Desta forma, o objetivo deste trabalho foi avaliar um poss?vel efeito modulador de GSH sobre a libera??o de GABA mediada por glutamato em retinas de embri?o de galinha. Para isso, utilizamos como modelo experimental tecido retiniano ?ntegro de embri?o de galinha, com sete ou oito dias de desenvolvimento. Nos ensaios de libera??o de GABA, as retinas foram tratadas com GSH (100 e 500 ?M); glutamato (50 e 500 ?M) e Butionina Sulfoximina (BSO), inibidor da s?ntese de glutationa, (50 ?M) por 15 minutos, e os n?veis de GABA liberado para o meio extracelular foram quantificados por Cromatografia L?quida de Alta Efic?cia (CLAE). Para experimentos de libera??o de compostos ti?is (?SH)...

Modula??o dos sistemas GABA?rgico e glutamat?rgico na secre??o hipotal?mica de ocitocina sob condi??es hiperosm?ticas

GRIS?LIA, Alan Barroso Ara?jo
Fonte: Universidade Federal do Pará Publicador: Universidade Federal do Pará
Tipo: Tese de Doutorado
POR
Relevância na Pesquisa
37.11%
Em mam?feros, a osmolalidade do flu?do extracelular ? o par?metro mais importante na manuten??o do balanco hidroeletrolitica. Deste modo, varia??es de osmolalidade s?o detectadas por c?lulas hipotal?micas especializadas, iniciando assim uma sinaliza??o neuroqu?mica, com envolvimento dos sistemas glutam?tergicos e GABA?rgico, a qual pode desencadear a secre??o da ocitocina. Entretanto, o modo como a rela??o dos amino?cidos GABA e glutamato pode modular a libera??o de ocitocina durante a hiperosmolalidade ainda ? pouco compreendida. Neste contexto, o objetivo do presente estudo foi caracterizar o efeito do meio hipert?nico sobre os n?veis extracelulares de GABA e glutamato e sua rela??o com a libera??o de ocitocina em prepara??es de hipot?lamo in vitro. Para tal, Ratos Wistar Machos (270-300g) foram mantidos em condi??es padr?es de laborat?rio. E ap?s decapita??o o c?rebro foi retirado rapidamente, os fragmentos hipotal?micos foram imediatamente dissecados em Krebs Ringer Bicarbonato Glicose gelado (KRBG) e colocados no sistema de perinfus?o com solu??o de KRBG isot?nica (280 mOsm/Kg H?O) fluxo de 0.5-1.0 ml/min, foram feitas as coletas a cada minuto durante 15 min. O est?mulo hipert?nico (340 mOsm/Kg H?O) ocorreu por 3 minutos. As dosagens de glutamato...

GABA and glutamate transporters: new events and function in the vertebrate retina

NASCIMENTO, Jos? Luiz Martins do; SAWADA, Luis Armando; OLIVEIRA, Karen Renata Matos; CRESPO L?PEZ, Maria Elena; SILVA, Anderson Manoel Herculano Oliveira da; HAMOY, Mois?s; SILVA, Consuelo Yumiko Yoshioka e; BASTOS, Gilmara de Nazareth Tavares; PANTOJA,
Fonte: Universidade Federal do Pará Publicador: Universidade Federal do Pará
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
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The neural retina is a highly complex tissue composed of excitatory and inhibitory neurons and glial cells. Glutamate, the main excitatory neurotransmitter, mediates information transfer from photoreceptors, bipolar cells, and ganglion cells, whereas interneurons, mainly amacrine and horizontal cells, use ?-aminobutyric acid (GABA), the main inhibitory neurotransmitter. In this review we place an emphasis on glutamate and GABA transporters as highly regulated molecules that play fundamental roles in neurotransmitter clearance, neurotransmitter release, and oxidative stress. We pharmacologically characterized glutamate transporters in chicken retina cells and identified two glutamate transporters: one Na+-dependent transporter and one Na+-independent transporter. The Na+-dependent uptake system presented characteristics related to the high-affinity xAG- system (EAAT1), and the Na+-independent uptake system presented characteristics related to the xCG- system, which highly contributes to glutamate transport in the retina. Glutamate shares the xCG- system with another amino acid, L-cysteine, suggesting the possible involvement of glutathione. Both transporter proteins are present mainly in M?ller glial cells. GABA transporters (GATs) mediate high-affinity GABA uptake from the extracellular space and terminate the synaptic action of GABA in the central nervous system. GABA transporters can be modulated by molecules that act on specific sites to promote transporter phosphorylation and dephosphorylation. In addition to a role in the clearance of GABA...

Couplage du récepteur à sept domaines transmembranaires GABA-B1 aux voies intracellulaires de signalisation en absence de GABA-B2

Richer, Maxime
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
FR
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37.2%
Le GABA est le principal neurotransmetteur inhibiteur du SNC et est impliqué dans le développement du cerveau, la plasticité synaptique et la pathogénèse de maladies telles que l’épilepsie, les troubles de l’anxiété et la douleur chronique. Le modèle actuel de fonctionnement du récepteur GABA-B implique l’hétérodimérisation GABA-B1/B2, laquelle est requise au ciblage à la surface membranaire et au couplage des effecteurs. Il y est cependant des régions du cerveau, des types cellulaires et des périodes du développement cérébral où la sous-unité GABA-B1 est exprimée en plus grande quantité que GABA-B2, ce qui suggère qu’elle puisse être fonctionnelle seule ou en association avec des partenaires inconnus, à la surface cellulaire ou sur la membrane réticulaire. Dans le cadre de cette thèse, nous montrons la capacité des récepteurs GABA-B1 endogènes à activer la voie MAPK-ERK1/2 dans la lignée dérivée de la glie DI-TNC1, qui n’exprime pas GABA-B2. Les mécanismes qui sous-tendent ce couplage demeurent mal définis mais dépendent de Gi/o et PKC. L’immunohistochimie de récepteurs endogènes montre par ailleurs que des anticorps GABA-B1 dirigés contre la partie N-terminale reconnaissent des protéines localisées au RE tandis des anticorps C-terminaux (CT) marquent une protéine intranucléaire. Ces données suggèrent que le domaine CT de GABA-B1 pourrait être relâché par protéolyse. L’intensité des fragments potentiels est affectée par le traitement agoniste tant en immunohistochimie qu’en immunobuvardage de type western. Nous avons ensuite examiné la régulation du clivage par le protéasome en traitant les cellules avec l’inhibiteur epoxomicine pendant 12 h. Cela a résulté en l’augmentation du marquage intranucléaire de GABA-B1-CT et d’un interacteur connu...

L-Glutamate uptake, decarboxylation to -aminobutyric acid and GABA efflux in isolated Asparagus sprengeri mesophyll cells

Chung, Induk.
Fonte: Brock University Publicador: Brock University
Tipo: Electronic Thesis or Dissertation
ENG
Relevância na Pesquisa
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Addition of L-glutamate caused alkalinization of the medium surrounding Asparagus spreng.ri mesophyll cells. This suggests a H+/L-glutmate symport uptake system for L-glutamate. However stoichiometries of H+/L-glutamate symport into Asparagus cells were much higher than those in other plant systems. Medium alkalinization may also result from a metabolic decarboxylation process. Since L-glutmate is decarboxylated to r-amino butyric acid (SABA) in this system, the origin of medium alkalinization was reconsidered. Suspensions of mechanically isolated and photosyntheically competent Asparagus sprengeri mesophyll cells were used to investigate the H+/L-glutamate symport system, SABA production, GABA transport, and the origin of L-glutamate dependent medium alkalinization. The major results obtained are summarized as follows: 1. L-Glutamate and GABA were the second or third most abundant amino acids in these cells. Cellular concentrations of L-glutamate were 1.09 mM and 1.31 mM in the light and dark, respectively. Those of SABA were 1.23 mM and 1.17 mM in the light and dark, respectively. 2. Asparagine was the most abundant amino acid in xylem sap and comprised 54 to 68 1. of the amino acid pool on a molar basis. GABA was the second most abundant amino acid and represented 10 to 11 1. of the amino acid pool. L-Slutamate was a minor component. 3. A 10 minute incubation with 1 mM L-glutamate increased the production of GABA in the medium by 2...

Uptake and release of [H-3]GABA in human dental pulp

Nassery, K.; Marino, V.; Parker, D.
Fonte: Pergamon-Elsevier Science Ltd Publicador: Pergamon-Elsevier Science Ltd
Tipo: Artigo de Revista Científica
Publicado em //2007 EN
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37.12%
The purpose of this study was to determine whether (a) an uptake system for gamma-aminobutyric acid (GABA) exists in human dental pulp, (b) GABA can be released from nerves in this tissue, and (c) GABA(B) autoreceptors modulate release of this transmitter. Segments of vital pulp were incubated in [(3)H]GABA (0.1-10 microM) for up to 120 min, washed, and the retained [(3)H] extracted and assayed. Some tissues were treated with GABA uptake inhibitors (nipecotic acid or NO-711) prior to incubation. At concentrations of 0.1 and 1.0 microM the uptake of [(3)H]GABA was saturated after 90 min of incubation. At 10 microM, at least two uptake compartments were apparent, and the amount of [(3)H]GABA retained was five-fold greater than 0.1 microM. The uptake inhibitors reduced [(3)H]GABA accumulation by more than 80%. In the release study, pulp was incubated in [(3)H]GABA (0.5 microM) for 90 min, and superfused with Krebs solution containing NO-711 (5 microM). Electrical stimulation increased the overflow of [(3)H]; a GABA(B) autoreceptor agonist (baclofen) inhibited, whilst an antagonist, Sch 50911, enhanced this release. The effects of baclofen were reversed by Sch 50911. These results imply that GABA can be taken up and bound firmly in compartments within human dental pulp...

The CGP7930 analogue 2,6-di-tert-butyl-4-(3-hydroxy-2-spiropentylpropyl)-phenol (BSPP) potentiates baclofen action at GABA(B) autoreceptors

Parker, D.; Marino, V.; Ong, J.; Puspawati, N.; Prager, R.
Fonte: Blackwell Publishing Asia Publicador: Blackwell Publishing Asia
Tipo: Artigo de Revista Científica
Publicado em //2008 EN
Relevância na Pesquisa
37.02%
The pharmacological actions of 2,6-di-tert-butyl-4-(3-hydroxy-2-spiropentylpropyl)-phenol (BSPP), a putative presynaptic GABA(B) receptor modulator, were examined in electrically stimulated rat neocortical brain slices preloaded with [3H]-GABA or [3H]-glutamic acid. At 10 mmol/L, BSPP inhibited the release of [3H]-GABA in the presence of baclofen, but not that of [3H]-glutamic acid. This effect was sensitive to the GABA(B) receptor antagonist (+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid (Sch 50911). Alone, BSPP had no effect on the release of [3H]-GABA or [3H]-glutamic acid. It is concluded that BSPP selectively potentiates the action of baclofen at GABA(B) autoreceptors, but not heteroreceptors and may be a useful ligand to discriminate between presynaptic GABA(B) receptor subtypes.; David AS Parker, Victor Marino, Jennifer Ong, Ni Made Puspawati and Rolf H Prager; The definitive version may be found at www.wiley.com

(R)-(3-Amino-2-fluoropropyl) Phosphinic Acid (AZD3355), a Novel GABA(B) Receptor Agonist, Inhibits Transient Lower Esophageal Sphincter Relaxation through a Peripheral Mode of Action

Lehmann, A.; Antonsson, M.; Holmberg, A.; Blackshaw, L.; Branden, L.; Brauner-Osborne, H.; Christiansen, B.; Dent, J.; Elebring, T.; Jacobson, B.M.; Jensen, J.; Mattsson, J.; Nilsson, K.; Oja, S.; Page, A.; Saransaari, P.; von Unge, S.
Fonte: Amer Soc Pharmacology Experimental Therapeutics Publicador: Amer Soc Pharmacology Experimental Therapeutics
Tipo: Artigo de Revista Científica
Publicado em //2009 EN
Relevância na Pesquisa
37.07%
Gastroesophageal reflux disease (GERD) affects >10% of the Western population. Conventionally, GERD is treated by reducing gastric acid secretion, which is effective in most patients but inadequate in a significant minority. We describe a new therapeutic approach for GERD, based on inhibition of transient lower esophageal sphincter relaxation (TLESR) with a proposed peripherally acting GABA(B) receptor agonist, (R)-(3-amino-2-fluoropropyl)phosphinic acid (AZD3355). AZD3355 potently stimulated recombinant human GABA(B) receptors and inhibited TLESR in dogs, with a biphasic dose-response curve. In mice, AZD3355 produced considerably less central side effects than the prototypical GABA(B) receptor agonist baclofen but evoked hypothermia at very high doses (blocked by a GABA(B) receptor antagonist and absent in GABA(B)-/- mice). AZD3355 and baclofen differed markedly in their distribution in rat brain; AZD3355, but not baclofen, was concentrated in circumventricular organs as a result of active uptake (shown by avid intracellular sequestration) and related to binding of AZD3355 to native GABA transporters in rat cerebrocortical membranes. AZD3355 was also shown to be transported by all four recombinant human GABA transporters. AR-H061719 [(R/S)-(3-amino-2-fluoropropyl)phosphinic acid]...

Die Hemmung der GABA-Wiederaufnahme im Zentralen Nervensystem: Ein Prinzip für neue Wirkstoffe in der Anästhesie?; Impairing GABA uptake in the central nervous system: a new route to anesthesia?

Razik, Daniel Simon
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
DE_DE
Relevância na Pesquisa
37.16%
Viele klinisch gebräuchliche Anästhetika vermindern die Aktivität von Nervenzellen in Gehirn und Rückenmark, indem sie GABA(A)-Rezeptoren, Zielstrukturen des hemmenden Botenstoffs gamma-Aminobuttersäure (GABA), positiv modulieren. Ein anderer, bisher jedoch kaum untersuchter Mechanismus, zentralnervöse Hemmung zu verstärken, besteht darin, die Wiederaufnahme von GABA zu hemmen. In der vorliegenden Arbeit wurde untersucht, wie eine Hemmung der Wiederaufnahme von GABA durch NO-711 spontane neuronale Aktivität im Neokortex in vitro beeinflusst und inwieweit sich diese Effekte von den in der Literatur beschriebenen Wirkungen gebräuchlicher Anästhetika unterscheiden. Extrazelluläre Messungen in organotypischen Schnittkulturen, deren Spontanaktivität durch Zustände hoher (Up states) und niedriger (Down states) Aktivität charakterisiert ist, zeigten mit steigender NO-711-Konzentration eine Reduktion der mittleren Feuerrate (EC50 = 34,07 nM), der relativen Zeitdauer, in der sich der Neokortex im aktiven Zustand befand (RelZeitaktiv, EC50 = 37,15 nM) und der mittleren Länge aktiver Phasen (Burstlänge, EC50 = 14,33 nM). Die Feuerraten innerhalb der späten Phase der Up states (100 – 500 ms nach Beginn eines Up states) nahmen konzentrationsabhängig ab...

Le GABA comme marqueur de récupération suite à une commotion cérébrale dans le sport ?

Tremblay, Sara
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
FR
Relevância na Pesquisa
37.12%
L’association démontrée récemment entre les commotions cérébrales dans le sport et le développement possible de maladies neurodégénératives a suggéré la possibilité que des altérations persistantes soient présentes dans le cerveau de l’athlète commotionné. En fait, des altérations neurophysiologiques ont récemment été révélées au sein du cortex moteur primaire (M1) d’athlètes ayant un historique de commotions via la stimulation magnétique transcrânienne (SMT). Plus précisément, la période silencieuse corticale (PSC), une mesure d’inhibition liée aux récepteurs GABAB, était anormalement élevée, et cette hyper-inhibition était présente jusqu’à 30 ans post-commotion. La PSC, et possiblement le GABA, pourraient donc s’avérer des marqueurs objectifs des effets persistants de la commotion cérébrale. Toutefois, aucune étude à ce jour n’a directement évalué les niveaux de GABA chez l’athlète commotionné. Ainsi, les études cliniques et méthodologiques composant le présent ouvrage comportent deux objectifs principaux: (1) déterminer si l’inhibition excessive (GABA et PSC) est un marqueur des effets persistants de la commotion cérébrale; (2) déterminer s’il est possible de moduler l’inhibition intracorticale de façon non-invasive dans l’optique de développer de futurs avenues de traitements. L’article 1 révèle une préservation des systèmes sensorimoteurs...

Is GABA involved in regulating plant growth and development? /

Zhang, Guijin.
Fonte: Brock University Publicador: Brock University
Tipo: Electronic Thesis or Dissertation
ENG
Relevância na Pesquisa
37.16%
Rapid and large accumulation of GABA (y-aminobutyric acid) in response to a number of plant stresses has been well documented. But the role(s) of GABA in plants is not well defined. In recent years, the possibility of GABA involvement in regulating plant growth and development has been raised. In the present study, this possibility was examined. First, to rapidly and accurately determine GABA levels in plant tissues, a spectrometric method for GABA determination was developed based on a commercially available enzyme Gabase. Seventy mM LaCb almost completely removed water-soluble pigments from plant tissues which greatly interfere with the absorbance reading at 340nm. Inactivation of GAD (glutamate decarboxylase) by immediately adding methanol to a frozen plant tissue powder was suggested to prevent GABA production during extraction. The recovery of GABA with this method was approximately 100%. Second, the relationship between GABA levels and hypocotyl elongation in soybean seedlings was analyzed using different approaches to regulate in vivo GABA levels and the elongation of hypocotyls. The following major observations were made. (1) Mechanical stimulation by stroking elevated GABA levels and concurrently induced a rapid and significant reduction in hypocotyl elongation. (2) External GABA was demonstrated to penetrate into the hypocotyls using '*C-GABA. Application of external GABA elevated in vivo GABA levels...

Alteration of GABA AR trafficking in epilepsy

Vieira, Ricardo da Costa Barbedo
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Dissertação de Mestrado
ENG
Relevância na Pesquisa
37.04%
A epilepsia é uma patologia crónica caracterizada por ataques epiléticos espontâneos. Esta patologia afeta cerca de 65 milhões de pessoas no mundo inteiro, de todas as idades e ambos os géneros. Pensa-se que a génese e/ou propagação dos ataques epiléticos tem origem na hiperexcitabilidade neuronal. No sistema nervoso central, o balanço entre a atividade excitatória e inibitória é maioritariamente mediada pelo glutamato, um neurotransmissor excitatório, e pelo ácido gama-aminobutírico (GABA), um neurotransmissor inibitório. O GABA atua, em parte, através da ativação de recetores de GABA do tipo A (GABAAR), os quais são, na sua grande parte, constituídos por duas subunidades α, duas β e uma subunidade γ2. Os GABAARs apresentam uma grande mobilidade na membrana, podendo deslocar-se entre as regiões sinápticas e extra-sinápticas. A acumulação dos GABAARs nas sinapses inibitórias é regulada pela proteína scaffold gefirina, a qual desempenha um papel importante no controlo da neurotransmissão GABAérgica rápida. A expressão superficial dos recetores GABAA é também influenciada pela taxa de internalização, a qual ocorre em regiões extra-sinápticas, assim como por mecanismos de regulação intracelular que determinam a taxa de reciclagem. Ataques epiléticos simples ou recorrentes provocam uma desregulação das sinapses GABAérgicas a diferentes níveis. Porém...

GABA y receptores GABA B en el eje reproductivo: su relación con GnRH y kisspeptinas; GABA and GABA B receptors in the reproductive axis: its relationship with GnRH and kisspeptins

Di Giorgio, Noelia Paula
Fonte: Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires Publicador: Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires
Tipo: info:eu-repo/semantics/doctoralThesis; tesis doctoral; info:eu-repo/semantics/publishedVersion Formato: application/pdf
Publicado em //2013 SPA
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Kisspeptina, GnRH y GABA juegan un papel fundamental en la regulación del eje gonadotrófico, si bien la interacción entre ellos está poco caracterizada. Estudios previos en ratones carentes del RGABAB funcional (GABAB1KO) sugerían alteraciones reproductivas, principalmente en la hembra. Nuestra hipótesis fue que GABA, a través de sus RGABAB, interviene en la regulación de la reproducción impactando sobre los sistemas GnRH/kisspeptina en el cerebro, durante el desarrollo y en la adultez. Demostramos por primera vez la co‐localización del RGABAB1 en neuronas Kiss1 del AVPV/PeN y ARC. La falta de un RGABAB funcional impacta diferencialmente según la edad evaluada. En ratones de 4 días de edad los cambios se observan en el hipotálamo medio basal, mientras que en ratones adultos aparecen en el hipotálamo anterior. Sin embargo, no se deberían a alteraciones hipotalámicas de Kiss1 ni a los niveles de esteroides circulantes. Además, los ratones GABAB1KO adultos presentaron un aumento drástico de Kiss1 en áreas extra hipotalámicas (MeA, BNST y Septum) relacionadas con la reproducción y la conducta sexual. En conclusión, GABA, a través de sus RGABAB, interactuaría con GnRH y kisspeptina en la regulación del eje gonadotrófico de manera diferencial durante el desarrollo y entre los sexos...

Modulación por óxido nítrico de receptores ionotrópicos de GABA; Nitric oxide modulation of ionotropic GABA Receptors

Gasulla, Javier
Fonte: Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires Publicador: Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires
Tipo: info:eu-repo/semantics/doctoralThesis; tesis doctoral; info:eu-repo/semantics/publishedVersion Formato: application/pdf
Publicado em //2014 SPA
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El NO es una molécula altamente difusible y reactiva producida en el sistema nervioso que actúa como mensajero neuronal y participa en procesos fisiológicos y patológicos. El NO modula la actividad de numerosos receptores de neurotransmisores y canales iónicos. En particular, los GABAARs pueden ser modulados por agentes rédox y por NO, aunque los efectos y mecanismos de este último no están claros. En esta tesis, caracterizamos los efectos del NO sobre GABAρ1Rs expresados de forma heteróloga y estudiamos la actividad de los GABAARs fásicos y tónicos de células piramidales en rebanadas de hipocampo con distintos niveles de NO. Los receptores homoméricos GABAρ1 se expresaron en ovocitos de Xenopus laevis, y las respuestas evocadas por GABA se registraron electrofisiológicamente, en presencia y ausencia de donantes de NO. Las respuestas se potenciaron significativamente por el NO de forma rápida, reversible y dosis-dependiente. El bloqueo químico de las cisteínas mediante reactivos selectivos para sulfhidrilos previno la potenciación por NO, indicando que las cisteínas participan de la modulación. Cada subunidad ρ1 tiene solo tres cisteínas, las dos extracelulares que forman el cys-loop (C177 y C191) y una intracelular (C364). El reemplazo por alanina de la C364 no modificó los efectos del NO sobre el receptor...

Differential effects of phosphonic analogues of GABA on GABAB autoreceptors in rat neocortical slices

Ong, J.; Marino, V.; Parker, D.; Kerr, D.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
Publicado em //1998 EN
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The effects of five phosphonic derivatives of GABA on the release of [3H]-GABA from rat neocortical slices, preloaded with [3H]-GABA, were investigated. Phaclofen and 4-aminobutylphosphonic acid (4-ABPA) increased the overflow of [3H] evoked by electrical stimulation (2 Hz) in a concentration-dependent manner, with similar potencies (phaclofen EC50=0.3 mmol/l, 4-ABPA EC50=0.4 mmol/l). At 3 mmol/l, phaclofen increased the release of [3H]-GABA by 82.6+/-8.6%, and 4-ABPA increased the release by 81.3+/-9.0%. 2-Amino-ethylphosphonic acid (2-AEPA) increased the overflow of [3H] by 46.8+/-10.9% at the highest concentration tested (3 mmol/l). In contrast, the lower phosphonic homologue 3-aminopropylphosphonic acid (3-APPA), and 2-amino-2-(p-chlorophenyl)-ethylphosphonic acid (2-CPEPA), a baclofen analogue, did not modify the stimulated overflow. These results suggest that phaclofen, 4-ABPA and 2-AEPA are antagonists at GABA(B) autoreceptors, the latter being the weakest antagonist, whilst neither 3-APPA nor 2-CPEPA are active at these receptors. Since phaclofen, 4-ABPA and 2-CPEPA are antagonists and 3-APPA a partial agonist/antagonist on GABA(B) heteroreceptors, the lack of effect of 3-APPA and 2-CPEPA on [3H]-GABA release in this study suggests that GABA(B) autoreceptors may be pharmacologically distinct from the heteroreceptors.