Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników

Znaleziono wyników: 16

Liczba wyników na stronie
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników

Wyniki wyszukiwania

Wyszukiwano:
w słowach kluczowych:  N-methyl-D-aspartate
help Sortuj według:

help Ogranicz wyniki do:
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
The large microtubule-associated/Ca2+-signalling protein p600 (also known as UBR4) is required for hippocampal neuronal survival upon Ca2+ dyshomeostasis induced by glutamate treatment. During this process, p600 prevents aggregation of the Ca2+/calmodulin-dependent kinase IIα (CaMKIIα), a proxy of neuronal death, via direct binding to calmodulin in a microtubuleindependent manner. Using photoconductive stimulation coupled with live imaging of single neurons, we identified a distinct mechanism of prevention of CaMKIIα aggregation by p600. Upon direct depolarization, CaMKIIα translocates to microtubules. In the absence of p600, this translocation is interrupted in favour of a sustained self-aggregation that is prevented by the microtubule-stabilizing drug paclitaxel. Thus, during photoconductive stimulation, p600 prevents the aggregation of CaMKIIα by stabilizing microtubules. The effectiveness of this stabilization for preventing CaMKIIα aggregation during direct depolarization but not during glutamate treatment suggests a model wherein p600 has two modes of action depending on the source of cytosolic Ca2+.
It was shown in this study that isolated porcine coronary arteries (PCA) contracted by depolarization with high Ko or by histamine are dose-dependently relaxed by glutamic acid, aspartic acid, N-methyl-asparate (NMDA) and γ-aminobutyric acid (GABA). Zn2+ was also shown to relax dose-dependently PCA contractions induced by 50 mM KCl with an ED50 value of about 1.5 mM and to inhibit dose-dependently histamine-induced contractions, shifting ED50 values from 6μM to 40 μM, not affecting however corresponding cumulative concentration-response (CCR) curves established for acetylcholine-induced contractions. Furthermore, since Zn2+ ions are co-localized in many glutamatergic synapses of the central nervous system, it has been postulated in analogy to glutamate neurotoxicity that perturbations of the synaptic zinc concentrations might be a triggering factor in several cerebral diseases, such as ischemic strokes and sustained seizures. Unfortunately, little is known so far about effects of glutamate and zinc ions on the vascular tone. Although the nature of the glutamatergic receptors occurring in the blood vessels investigated in this study remains unclear, the results suggest that glutamate and Zn2+ ions interact with voltage-gated as well with ligand-operated Ca-channels. An interesting aspect might be the putative role of glutamate and zinc as long-term toxic agents in the early steps of the pathomechanisms leading to degenerative vascular lesions.
The aim of this in vivo microdialysis study was to characterise the regulation of prostaglandin D2 (PgD2) synthesis by NMDA receptors in the rabbit hippocampus in relation to changes in extracellular Ca concentration ([Ca ]e) and nitric oxide (NO) levels. Samples of dialysate were analysed for changes in PgD2 concentration, in [Ca ]e and in the level of NO. The results demonstrated that a 20-min pulse application of 0.1 - 2.5 mM NMDA via a microdialysis probe induced a prolonged stimulation of PgD2 release that was sensitive to competitive NMDA receptor antagonists. An inhibitor of voltage-sensitive Na+ channels, tetrodotoxin, did not influence this effect but significantly suppressed basal PgD2 production, whereas a NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), prevented NMDA-evoked NO release and inhibited NMDA-induced PgD2 release in an L-arginine-sensitive manner. NO donors, S-nitroso-N-acetylpenicillamine and sodium nitroprusside, stimulated PgD2 release. NMDA-evoked decrease in [Ca2+]e was insensitive to TTX and L-NAME. These results demonstrate an in vivo NMDA receptor-mediated modulation of PgD2 synthesis in the brain, in which NO participates.
A brief period of antecedent oxygen breathing enhances the ventilatory response to hypoxia. The mechanisms of this phenomenon are uncertain and have been variably linked to the central glutamatergic or nitrergic pathways. In the present study we put a question of how blockade of either neurotransmitter pathway would compare with the concurrent blockade of them both in terms of the enhancement of posthyperoxic hypoxic ventilation. The study was performed on the anesthetized, vagotomized, spontaneously breathing rats divided into the following experimental groups: control NaCl-treated, glutamate blocker 2-amino-5-phosphonopentanoic acid (AP5)-treated, nitric oxide synthase blocker 7-nitroindazol (7NI)-treated, and AP5+7NI-treated. The protocol consisted of measuring the ventilatory response to 12% O2, a steady-state poikilocapnic hypoxia, undertaken in three consecutive conditions in each animal: the initial control, 25 min after injection of a given chemical agent, and then after a 15-min period of oxygen breathing. Respiration was evaluated from the diaphragmatic EMG signal. We found that the posthyperoxic hypoxic ventilatory enhancement was but partially dampened by either AP5 or 7NI. Concurrent administration of the two blockers further diminished, but did not abolish, the hypoxic ventilatory enhancement. We conclude that although the glutamate-NO system accounts for an appreciable part of the posthyperoxic hypoxic ventilatory enhancement, other, as yet unclear, mechanisms contribute as well. These mechanisms may be worth exploring given the substantial enhancing effect the antecedent oxygen has on hypoxic hyperventilation.
6
84%
The intergeniculate leaflet (IGL) has been shown to be a functional constituent of the circadian timing system. The IGL receives a monosynaptic input from the retina and is known to mediate some of the effects of light on the circadian clock. In the majority of retinal ganglion cells, glutamate functions as an excitatory neurotransmitter. The effect of monosodium glutamate and N-methyl-D-aspartate (NMDA), on the extracellularly recorded discharge activity of IGL neurons was studied in vitro. The application of monosodium glutamate induced either an excitatory, a biphasic or an inhibitory response. Application of NMDA induced an excitatory response in the majority of tested neurons. To determine the role of NMDA receptors in the response to glutamate application, the selective antagonist of NMDA receptors- AP-5, was applied to the incubation medium. The presence of AP-5 reduced the response of the IGL cells to focal application of glutamate and completely blocked their responsiveness to NMDA. To clarify whether GABAergic interneurons are involved in mediation of the inhibitory effects of glutamate, we repeated our experiments in the presence of bicuculline in the incubation medium. Since bicuculline did not influence the observed inhibitory effects, the involvement of GABAA receptors was excluded. The present study provides the first electrophysiological evidence that neurons in the rat IGL, respond to glutamate probably through NMDA receptors. However, our results also suggest that other types of glutamate receptors may play an additional role in mediating the action of this excitatory amino acid on the IGL neurons.
The NADPH-diaphorase (as a neuronal NO-synthase) reactivity in the medullary structures of the respiratory rhythm (RR) generator and the role of NO in the regulation of respiratory activity in the phrenic nerve of artificially superfused semi-isolated medulla-spinal cord preparations were investigated in newborn rats. NADPH-diaphorase positive neurons were found in all nuclei of both dorsal and ventral respiratory groups of neurons. The maximal density of stained cells was present within the rostral part of the ventrolateral medulla (VLM), in the region of the lateral paragigantocellular reticular nucleus. It was found that endogenous NO mediates the mechanism of tonic inhibitory control of the RR frequency located in the rostral VLM under normal and hypoxic conditions, and appears to be involved in generation of the basic RR by the more caudal structures of VLM. It was shown that NO biosynthesis mediates the effect of NMDA receptors activation on the RR.
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.