This study examined the relationship between the affinity of glutamate agonists for the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the characteristics of the physiological responses elicited by endogenous activation of the AMPA receptors. We tested the effects of chaotropic ions on [3H]AMPA binding in synaptic membranes as well as on synaptic responses elicite...

Little is known about the mechanisms that regulate the number of ionotropic glutamate receptors present at excitatory synapses. Herein, we show that GluR1-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) are removed from the postsynaptic plasma membrane of cultured hippocampal neurons by rapid, ligand-induced endocytosis. Although endocytosis of AMPA...

In this study, we examined the effects of a novel, water-soluble, putative competitive AMPA receptor antagonist, 1,2,3,6,7, 8-hexahydro-3-(hydroxyimino)-N,N,7-trimethyl-2-oxobenzo[2,1- b:3, 4-c']dipyrrole-5-sulfonamide (NS-257) on AMPA, kainate and NMDA receptors using the two-electrode voltage-clamp technique in Xenopus oocytes. All glutamate receptor subtypes were inhibited by NS-257 in a vol...

Exogenous phospholipases have been used extensively as tools to study the role of membrane lipids in receptor mechanisms. We used in vitro quantitative autoradiography to evaluate the effect of phospholipase A2 (PLA2) on N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in rat brain. PLA2 pretreatment induced a significant increase in alpha-[3H]amino-3-hydroxy-5-methyl-isoxazole-4-pr...

All ionotropic glutamate receptor (iGluR) subunits analyzed so far are heavily N-glycosylated at multiple sites on their amino-terminal extracellular domains. Although the exact functional significance of this glycosylation remains to be determined, it has been suggested that N-glycosylation may be a precondition for the formation of functional ion channels. In particular, it has been argued th...

Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavalpha2delta1) has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavalpha2delta1 proteins i...

A fast perfusion system was used to apply excitatory amino acids to embryonic hippocampal neurons grown in dissociated culture and voltage clamped in the whole-cell recording configuration. Responses to quisqualic acid and DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA; a potent quisqualate-like agonist) showed rapid desensitization: at 100 microM the peak inward current dec...

Excitotoxicity, resulting from sustained activation of glutamate receptors of the N-methyl-d-aspartate (NMDA) subtype, is considered to play a causative role in the etiology of ischemic stroke and several neurodegenerative diseases. The NMDA receptor is therefore a target for the development of neuroprotective agents. Here, we identify an N-benzylated triamine (denoted as NBTA) as a highly sele...

The rat brain-derived neurotropic factor (BDNF) gene consists of four 5' exons linked to separate promoters and one 3' exon encoding the prepro-BDNF protein. To gain insights into the regulation of BDNF mRNA expression, probes specific for the different 5' exons were used to study the expression of BDNF mRNA in the brain. Following a systemic injection of the glutamate analog kainic acid, exon ...

Superfusion of hippocampal slices with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) antagonized kainate-induced bursts and bursts of unknown origin in the CA3 region. CNQX also increased the latency of and eventually blocked evoked bursts which persist following kainate washout. In contrast, D-(-)-2-amino-7-phosphonoheptanoic acid did not alter burst latency or block bursts unless applied subseq...