Glutamate is extensively and relatively uniformly distributed in the central nervous system (CNS) and its effects mediated by two distinct groups of receptors including Ionotropic and metabotropic glutamate receptors. Concentration of glutamate in the nervous system is much higher than in other tissues. Glutamate receptors play an important role in synaptic transmission, neural plasticity and n...

Glutamate is the most important excitatory neurotransmitter in the central nervous system which is involved in synaptic transmission, brain development, synaptic plasticity, learning, and memory. Normally, the enzymatic destruction of glutamate does not occur in the synaptic and extracellular space, but glutamate is removed through specific transporter proteins, leading to stabilization of glut...

Activation of N-methyl-d-aspartate (NMDA) receptors in the spinal dorsal horn neurons is a key process related to sensory transmission, neural plasticity, and pathogenesis of pain. In this study, we investigated how activation of NMDA receptors in spinal substantia gelatinosa neurons is regulated by glutamate re-uptake through glutamate transporters located in the astrocytic and neuronal plasma...

Glutamate transporters (GluTs) prevent the accumulation of glutamate and influence the occupancy of receptors at synapses. The ability of extrasynaptic NMDA receptors and metabotropic glutamate receptors to participate in signaling is tightly regulated by GluT activity. Astrocytes express the highest density of GluTs and dominate clearance away from these receptors; synapses that are not associ...

Glutamate released at synapses in the CA1 region of the hippocampus escapes the synaptic cleft and activates extrasynaptic targets; it also may "spill over" into neighboring synapses and activate receptors there. Glutamate transporters in glial membranes restrict extrasynaptic diffusion, but it is unclear whether neuronal glutamate transporters also limit transmitter diffusion and receptor acti...

Fast-acting neurotransmitters can exit the synaptic cleft and bind to extrasynaptic receptors. This process is modulated by transmitter uptake mechanisms (transporters). A new study focusing on glutamate-mediated transmission in the cerebellum describes the specific role of neuronal transporters in modulating the access of glutamate to extrasynaptic metabotropic glutamate receptors, and reveals...

Drug addiction has often been described as a "hijacking" of the brain circuits involved in learning and memory. Glutamate is the principal excitatory neurotransmitter in the brain, and its contribution to synaptic plasticity and learning processes is well established in animal models. Likewise, over the past 20 years the addiction field has ascribed a critical role for glutamatergic transmissio...

Objective(s): Glutamate is the most widespread neurotransmitter in the central nervous system and has several functions as a neuromodulator in the brain although in pathological conditions like ischemia it is excessively released causing cell death. Under physiological conditions, glutamate is rapidly scavenged from the synaptic cleft by excitatory amino-acid transport...

Signaling through glutamate receptors has been reported in human cancers, but the molecular mechanisms are not fully delineated. We report that in hepatocellular carcinoma and clear cell renal carcinoma cells, increased activity of hypoxia-inducible factors (HIFs) due to hypoxia or VHL loss-of-function, respectively, augmented release of glutamate, which was mediated by HIF-dependent expression...

Astrocytes have long been regarded as essentially unexcitable cells that do not contribute to active signaling and information processing in the brain. Contrary to this classical view, it is now firmly established that astrocytes can specifically respond to glutamate released from neurons. Astrocyte glutamate signaling is initiated upon binding of glutamate to ionotropic and/or metabotropic rec...