The N-methyl-D-aspartate (NMDA) type of glutamate receptor is a calcium-permeable ion channel with important functions in the physiology and pathology of the mammalian brain. NMDA receptors are critical for long-lasting, activity-induced changes in synaptic transmission, a process thought to be involved in learning and memory. NMDA receptors also control neuronal survival and cell death. How ca...

Overstimulation of NMDA-type glutamate receptors is believed to be responsible for neuronal death of the CNS in various disorders, including cerebral and spinal cord ischemia. However, the intrinsic and physiological mechanisms of modulation of these receptors are essentially unknown. Here we report that cholestane-3β,5α,6β-triol (triol), a major metabolite of cholesterol, is an endogenous neur...

Abstract The NMDA receptors (NMDARs) expressed by AII and A17 amacrine cells, the two main inhibitory interneurons of rod pathway microcircuit in mammalian retina, are exclusively extrasynaptic, activated ambient levels glutamate, molecularly distinct, with amacrines expressing GluN2B‐ GluN2A‐containing receptors, respectively. This important sensory thus provides a unique model to study activa...

Glutamate receptors and protein kinase C (PKC) may play significant roles in long-term potentiation in hippocampus. To clarify the regulatory involvement of PKC in the functions of glutamate receptors, we examined the effects of PKC activation on current response induced by the activation of each subtype of glutamate receptor in Xenopus oocytes injected with rat brain RNA. Treatment with the PK...

The mechanisms by which neurons die after cerebral ischemia and related conditions in vivo are unclear, but they are thought to involve voltage-dependent Na+ channels, glutamate receptors, and nitric oxide (NO) formation because selective inhibition of each provides neuroprotection. It is not known precisely what their roles are, nor whether they interact within a single cascade or in parallel ...

NMDA receptors are ionotropic glutamate receptors that mediate excitatory synaptic transmission and have been implicated in several neurological diseases. We have evaluated the mechanism of action of a class of novel subunit-selective NMDA receptor antagonists, typified by (E)-4-(6-methoxy-2-(3-nitrostyryl)-4-oxoquinazolin-3(4H)-yl)-benzoic acid (QNZ46). We found that QNZ46 inhibits NMDA recept...

Local protein synthesis in neuronal dendrites is critical for synaptic plasticity. However, the signaling cascades that couple synaptic activation to dendritic protein synthesis remain elusive. The purpose of this study is to determine the role of glutamate receptors and the mammalian target of rapamycin (mTOR) signaling in regulating dendritic protein synthesis in live neurons. We first charac...

Synaptic glutamate transients resulting from vesicular exocytosis are superimposed on a low baseline concentration of glutamate in the extracellular space. Reported values of baseline glutamate concentrations range up to 4 microM. If glutamate were present tonically at low micromolar concentrations, many receptors, especially the high-affinity NMDA receptors (NMDARs), would be activated or dese...

The accumulation of glutamate can excessively activate the N-methyl-d-aspartate (NMDA) receptors and cause excitotoxicity. Daphnetin (Dap), a coumarin derivative, is a protein kinase inhibitor that exhibits antioxidant and neuroprotective properties. However, little is known about the neuroprotective effects of Dap on glutamate-induced excitotoxicity. We evaluated the neuroprotective activities...

Human airway smooth muscle (HASM) exhibits enhanced contractility in asthma. Inflammation is associated with airway hypercontractility, but factors that underpin these features are not fully elucidated. Glutamate toxicity associated with increased plasma glutamate concentrations was observed in airway inflammation, suggesting that multisubunit glutamate receptors, N-methyl-d-aspartate receptors...