RESUMO
It has been established that neurons exposed to high concentrations of glutamate or other excitatory amino acids degenerate and die. Neuronal damage appears to be due to the activation of different types of glutamate receptors, among which the ionotropic N-methyl-D-aspartate (NMDA) type seems particularly involved, since its channel is permeable to Ca2+ and an increase in the cytoplasmic concentration of this cation promotes a chain of events leading to cell death. The mechanism of such glutamate receptor-mediated neurodegeneration has been defined as excitotoxicity, and several pieces of evidence suggest that this mechanism might contribute to the neuronal death associated with certain neurological disorders, such as ischemia, cerebral trauma and some chronic neurodegenerative diseases. A relevant question is whether the origin of endogenous extracellular glutamate is important for the induction of excitotoxicity. An excess of glutamate release, or a deficiency in its clearance from the synaptic cleft, which depends mainly on its transport by high affinity carriers, are potential sources for the accumulation of extracellular glutamate. In the present article some experimental results from our laboratory, aimed at obtaining information on this question, are reviewed. These experiments include the use of 4-aminopyridine, a convulsant drug that enhances the release of glutamate, and of some inhibitors of glutamate transport, in vivo and in neuronal cell cultures. The results obtained indicate that an increase of endogenous extracellular glutamate due to these procedures is not sufficient to induce neuronal death, at least under the experimental condition used.
Assuntos
4-Aminopiridina/efeitos adversos , Técnicas de Cultura de Células , Ácido Glutâmico/fisiologia , Ácido Glutâmico/toxicidade , Técnicas In Vitro , N-Metilaspartato/fisiologia , Degeneração Neural/fisiologiaRESUMO
Mammalian circadian rhythms are controlled by a biological clock located in the hypothalamic suprachiasmatic nuclei (SCN). This clock is entrained by light through a retinohypothalamic pathway that interacts with the SCN through glutamate neurotransmission. Light pulses during the subjective night induce phase shifts of behavioral rhythms, and also trigger intracellular changes such as the expression of immediate-early genes and activation of transcription factors. In this review, we present a model of the signal transduction pathway leading to photic synchronization of the circadian clock, including the activity of specific second messenger systems, gene expression, and interaction between potential agents capable of producing phase shifts.
Assuntos
Animais , Ritmo Circadiano/fisiologia , Luz , Núcleo Supraquiasmático/fisiologia , Relógios Biológicos/fisiologia , Transdução de Sinais/fisiologia , Aminoácidos Excitatórios/fisiologia , N-Metilaspartato/fisiologia , Transdução de SinaisRESUMO
Objetivos: Analizar toda la información publicada en los últimos diez años sobre el receptor al N-Metil-D-Aspartato (NMDA). Establecer una correlación farmaco-clínica con respecto a la modulación del dolor y determinar su importancia en anestesiología. Lugar: Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo. Base de datos: Base electrónica Medline de donde se seleccionaron todos los trabajos publicados en idioma inglés sobre el tema y búsqueda de información en castellano de lo publicado en los últimos 10 años. Estrategia de búsqueda: NMDA, dolor, modulación del dolor, protección cerebral. Discusión: Los receptores celulares son estructuras que permiten comandar el metabolismo íntimo de las células que los poseen. Estos interactúan en forma directa a través de un segundo mensajero citoplasmático. En el neuroeje de los mamíferos, se encuentran numerosas neuronas que contienen en su membrana el receptor al NMDA. El bloqueo de éste por drogas que actúan en forma competitiva o no competitiva, produciría analgesia, permitiría la modulación del estímulo doloroso y algunos trabajos demuestran su importancia como protectores cerebrales ante la isquemia. Conclusión: Los inhibidores de los receptores al NMDA como la dizocilpina, actualmente en fase experimental, o la ketamina, adquirirían un rol muy importante en nuestra especialidad en el manejo del dolor y la protección cerebral.