Excitatory amino acids and their receptors play an important role in both normal synaptic transmission and excitotoxic-mediated neuronal death. In the present investigation we have prepared a series of glutamate analogs and examined the pharmacological specificity with which they interact with excitatory amino acid receptors. Included within this group of compounds is a potent excitotoxic amino...

Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses. J. Neurophysiol. 80: 3336-3340, 1998. At central synapses occupation of glycine binding sites of N-methyl--aspartate receptors (NMDA-Rs) is a necessary prerequisite for the excitatory neurotransmitter glutamate to activate these receptors. There is conflicting evidence as to whether glycine binding sites nor...

Nitrous oxide (N2O; laughing gas) has been a widely used anesthetic/analgesic since the 19th century, although its cellular mechanism of action is not understood. Here we characterize the effects of N2O on excitatory and inhibitory synaptic transmission in microcultures of rat hippocampal neurons, a preparation in which anesthetic effects on monosynaptic communication can be examined in a setti...

Peptide growth factors such as the neurotrophins and fibroblast growth factors have potent effects on synaptic transmission, development, and cell survival. We report that chronic (hours) treatment with basic fibroblast growth factor (FGF-2) potentiates Ca(2+)-dependent N-methyl-D-aspartate (NMDA) receptor inactivation in cultured hippocampal neurons. This effect is specific for the NMDA-subtyp...

Human primary and clonal synovial cells were incubated with glutamate receptor agonists to assess their modulating influence on glutamate receptors N-methyl-d-aspartate (NMDA) NR1 and NR2 and inflammatory cytokines to determine potential for paracrine or autocrine (neurocrine) upregulation of glutamate receptors, as has been shown for bone and chondrocytes. Clonal SW982 synoviocytes constitutiv...

The purpose of the present study was to determine whether some of the age-related changes that occur in binding to the NMDA receptor complex can be accounted for by changes in subunit expression during the aging process. In situ hybridization for the NMDA subunits zeta1, epsilon1, and epsilon2, and receptor autoradiography, using the agonist glutamate and the competitive antagonist [(+/-)-2-car...

In Xenopus oocytes injected with rat brain mRNA, as in neurons, glycine greatly potentiated responses of the N-methyl-D-aspartate (NMDA) type of excitatory amino acid receptor. Injected oocytes generated a partially desensitizing inward current in response to NMDA with 30 nM added glycine. As the added glycine concentration was increased from 30 nM to 1 microM, the NMDA response was increased a...

N-methyl-d-aspartate (NMDA) receptors are the only neurotransmitter receptors whose activation requires two distinct agonists. Heterotetramers of two GluN1 and two GluN2 subunits, NMDA receptors are broadly distributed in the central nervous system, where they mediate excitatory currents in response to synaptic glutamate release. Pore opening depends on the concurrent presence of glycine, which...

N-methyl-D-aspartate (NMDA) receptors have been implicated in learning and memory. Many findings show that NMDA receptor antagonists impair memory. Few studies, however, have investigated the role of NMDA receptor agonists in mnemonic function. The present study examined the effects of nucleus basalis magnocellularis (nbm) injections of NMDA on memory. Rats were trained in a two-component doubl...

The role of the endogenous opioid peptide dynorphin (1-17) in regulating NMDA receptor-mediated synaptic currents was examined in guinea pig hippocampus. Schaffer collateral/commissural fiber-evoked NMDA synaptic currents were recorded using whole-cell patch-clamp techniques in CA3 pyramidal cells. Dynorphin was found to have dual effects on NMDA synaptic currents, increasing currents at low co...