Monocyte chemotactic protein 1 upregulates IL-1beta expression in human monocytes.

Monocyte chemotactic protein-1 (MCP-1) chemoattracts and activates monocytes. The nature of the genes that are transcriptionally activated in the monocytes by MCP-1 is not well understood. To identify such genes, human blood monocytes were incubated with or without MCP-1 for periods of 1, 4, and 12 h and the RNA extracted from these monocytes was subjected to differential display.

Solution structure of the sodium channel inactivation gate.

The sodium channel initiates action potentials by opening in response to membrane depolarization. Fast channel inactivation, which is required for proper physiological function, is mediated by a cytoplasmic loop proposed to occlude the ion pore via a hinged lid mechanism with the triad IFM serving as a hydrophobic "latch". The NMR solution structure of the isolated inactivation gate reveals a stably folded core comprised of an alpha-helix capped by an N-terminal turn, supporting a model in which the tightly folded core containing the latch motif pivots on a more flexible hinge region to occlude the pore during inactivation.

Functional consequences of NR2 subunit composition in single recombinant N-methyl-D-aspartate receptors.

Single-channel recordings were obtained from Chinese hamster ovary cells transfected with the N-methyl-D-aspartate (NMDA) receptor subunit NR1 in combination with NR2A, NR2B, NR2C, or NR2A/NR2B. NMDA-activated currents were recorded under control conditions and in the presence of a thiol reductant (DTT), an oxidant (5, 5'-dithio-bis[2-nitrobenzoic acid], DTNB), or the noncompetitive antagonist CP101,606 (CP). For all subunit combinations, DTT increased the frequency of channel opening when compared with DTNB.

Intrinsic redox properties of N-methyl-D-aspartate receptor can determine the developmental expression of excitotoxicity in rat cortical neurons in vitro.

The sensitivity of central neurons in culture to N-methyl-D-aspartate (NMDA) receptor-mediated cell death increases with development. In this study, we show that this phenomenon in vitro may be due, at least in part, to changes in the redox properties of the NMDA receptor itself. With increasing days in culture, NMDA-induced electrical responses in rat cortical neurons are less sensitive to dithiothreitol-induced potentiation and spontaneously oxidize less readily than in younger cells.

Trapping channel block of NMDA-activated responses by amantadine and memantine.

We investigated the mechanisms by which the antiparkinsonian and neuroprotective agents amantadine and memantine inhibit responses to N-methyl-D-aspartic acid (NMDA). Whole cell recordings were performed using cultured rat cortical neurons or Chinese hamster ovary (CHO) cells expressing NMDA receptors. Both amantadine and memantine blocked NMDA-activated channels by binding to a site at which they could be trapped after channel closure and agonist unbinding.