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301.
D B Pritchett H Sontheimer B D Shivers S Ymer H Kettenmann P R Schofield P H Seeburg 《Nature》1989,338(6216):582-585
Neurotransmission effected by GABA (gamma-aminobutyric acid) is predominantly mediated by a gated chloride channel intrinsic to the GABAA receptor. This heterooligomeric receptor exists in most inhibitory synapses in the vertebrate central nervous system (CNS) and can be regulated by clinically important compounds such as benzodiazepines and barbiturates. The primary structures of GABAA receptor alpha- and beta-subunits have been deduced from cloned complementary DNAs. Co-expression of these subunits in heterologous systems generates receptors which display much of the pharmacology of their neural counterparts, including potentiation by barbiturates. Conspicuously, however, they lack binding sites for, and consistent electrophysiological responses to, benzodiazepines. We now report the isolation of a cloned cDNA encoding a new GABAA receptor subunit, termed gamma 2, which shares approximately 40% sequence identity with alpha- and beta-subunits and whose messenger RNA is prominently localized in neuronal subpopulations throughout the CNS. Importantly, coexpression of the gamma 2 subunit with alpha 1 and beta 1 subunits produces GABAA receptors displaying high-affinity binding for central benzodiazepine receptor ligands. 相似文献
302.
Arginine vasopressin enhances pHi regulation in the presence of HCO3- by stimulating three acid-base transport systems 总被引:14,自引:0,他引:14
Growth factors raise intracellular pH (pHi) by stimulating Na+/H+ exchange in the absence of HCO3-. In mutant cells that lack the Na+/H+ exchange activity, this alkalinization does not occur, and the cells do not proliferate without artificial elevation of pHi. It has therefore been widely suggested that an early pHi increase is a necessary signal for mitogenesis. In the presence of HCO3- however, growth factors fail to raise pHi in A431 cells, renal mesangial cells and 3T3 fibroblasts. In mesangial cells, arginine vasopressin (AVP) raises pHi in the absence of HCO3-, but lowers it when HCO3- is present; growth is stimulated under both conditions. We report here that, in the presence of HCO3-, AVP stimulates two potent HCO3- transporters, as well as the Na+/H+ exchanger. These are the Na+-dependent and Na+-independent Cl-/HCO3- exchangers. Our results indicate that AVP causes acidification in the presence of HCO3- because, at the resting pHi, it stimulates Na+-independent Cl-/HCO3- exchange (which lowers pHi) more than it stimulates the sum of Na+/H+ exchange and Na+-dependent Cl-/HCO3- exchange (both of which raise pHi). The stimulation of three acid-base transporters by the growth factor AVP greatly enhances the ability of the cell to regulate pHi. 相似文献
303.
Clonal anergy induced in mature V beta 6+ T lymphocytes on immunizing Mls-1b mice with Mls-1a expressing cells 总被引:47,自引:0,他引:47
Tolerance to self-antigens has been shown to develop during ontogeny as a result of the clonal deletion of self-reactive T cells. Tolerance, or better 'nonresponsiveness', to specific antigens can also be induced in adult animals but the mechanism(s) involved are not well understood. Most murine T-helper cells that express the V beta 6 T-cell receptor gene segment are specific for Mls-1a antigens. We have therefore been able to use an anti-V beta 6 monoclonal antibody to follow the fate of Mls-1a specific T cells in adult Mls-1b mice made specifically unresponsive to Mls-1a. We show that the induced unresponsiveness is not due to clonal deletion, but rather to clonal anergy. The anergic V beta 6 T-helper cells express IL-2 receptors and undergo limited blastogenesis in vitro upon stimulation, but do not produce IL-2, in marked contrast to V beta 6 cells from naive mice. Our data appear to represent an in vivo correlate for the induction of anergy that has been observed in T-cell lines in vitro. 相似文献
304.
T-cell receptor delta-chain can substitute for alpha to form a beta delta heterodimer 总被引:11,自引:0,他引:11
Specific monoclonal antibodies have made possible the identification of two T-cell antigen receptor (TCR) heterodimers, alpha beta TCR and gamma delta TCR. Formation of these receptors is largely separated by the preferential pairing of alpha-TCR with beta and gamma-TCR with delta, the sequential rearrangement and expression of the TCR loci during thymic development and the deletion of the delta-loci either prior to or concomitant with alpha-rearrangement in alpha beta TCR cells. Here we show that delta-TCR can substitute for alpha in pairing with beta to form a beta delta heterodimer. This receptor is expressed on the cell surface of the T-leukaemia cell line DND41 as analysed with beta- and delta-specific monoclonal antibodies. We suggest that a variety of factors including, for example, the deletion of the delta-TCR loci, can now be understood as exclusion mechanisms operating to prevent not only the formation of gamma delta receptors, but also of beta delta T-cell receptors, thereby promoting the numerically dominant alpha beta TCR lineage. Nevertheless, some developing T-cells that do not rearrange the alpha-loci may express the beta delta TCR as described here. 相似文献
305.
Signal transduction through the CD4 receptor involves the activation of the internal membrane tyrosine-protein kinase p56lck 总被引:95,自引:0,他引:95
The CD4 T-cell surface antigen is an integral membrane glycoprotein of relative molecular mass 55,000 which binds class II major histocompatibility complex (MHC) molecules expressed on antigen presenting cells (APCs). It is thought to stabilize physical interactions between T cells and APCs (for a review, see ref. 1). Evidence is accumulating that suggests that CD4 can transduce an independent signal during T-cell activation. It has recently been shown that CD4 expressed on human and murine T cells is physically associated with the Src-related tyrosine protein kinase p56lck (refs 7, 8). These results indicate that CD4 can function as a signal transducer and suggest that tyrosine phosphorylation events may be important in CD4-mediated signalling. Here, we present evidence that cross-linking of the CD4 receptor induces a rapid increase in the tyrosine-specific protein kinase activity of p56lck and is associated with the rapid phosphorylation of one of the subunits (zeta) of the T-cell receptor complex on tyrosine residues. These data provide direct evidence for a specific CD4 signal transduction pathway that is mediated through p56lck and suggest that some of the tyrosine phosphorylation events detected during antigen-mediated T-cell activation may result from signalling through this surface molecule. 相似文献
306.
Vesicular removal by oligodendrocytes of membrane attack complexes formed by activated complement 总被引:15,自引:0,他引:15
N J Scolding B P Morgan W A Houston C Linington A K Campbell D A Compston 《Nature》1989,339(6226):620-622
Oligodendrocytes synthesize myelin in the central nervous system and maintain it in lamellar sheaths around axons. Techniques for studying oligodendrocyte development in vitro can be used, indirectly, to investigate the myelin injury that occurs in human and experimental demyelinating disease. Cell-mediated immune mechanisms are necessary but not sufficient to induce myelin damage in vivo; more recently complement has also been implicated in the pathogenesis both of multiple sclerosis and experimental allergic encephalomyelitis. Previously we have demonstrated that antibody-independent complement activation occurs in vitro at the oligodendrocyte surface. Here we show that the ensuing oligodendrocyte injury is reversible, and that recovery involves the release of membrane-attack complex-enriched vesicles from the surface of viable cells. The demonstration of morphologically and immunochemically identical vesicles in the cerebrospinal fluid of patients with multiple sclerosis suggests that reversible complement-mediated injury contributes to myelin damage in vivo. 相似文献
307.
308.
Three-dimensional crystal structures of Escherichia coli met repressor with and without corepressor 总被引:17,自引:0,他引:17
The three-dimensional crystal structure of met repressor, in the presence or absence of bound corepressor (S-adenosylmethionine), shows a dimer of intertwined monomers, which do not have the helix-turn-helix motif characteristic of other bacterial repressor and activator structures. We propose that the interaction of met repressor with DNA occurs through either a pair of symmetry-related alpha-helices or a pair of beta-strands, and suggest a model for binding of several dimers to met operator regions. 相似文献
309.
K. Ikemoto T. Utsunomiya M. A. Ball M. Kobayashi R. B. Pollard F. Suzuki Ph.D. 《Cellular and molecular life sciences : CMLS》1994,50(5):456-460
The antiviral activity of Shigyaku-to (TJS-109), a traditional Chinese herbal medicine, was investigated in mice infected with herpes simplex virus type 1 (HSV-1). TJS-109 is a combination of the medicinal plant extracts fromZingiberis siccatum rhizoma,Aconiti tuber andGlycyrrhizae radix in a specific proportion. Mice infected with a 10 LD50 dose of HSV-1 were treated with TJS-109 orally at doses of 1.25 to 20 mg/kg 2 days before, and 1 and 4 days after the infection. The treated groups had 80% (1.25 mg/kg), 40% (5 mg/kg) and 23% (20 mg/kg) mortality rates 25 days after the infection as compared with a 100% mortality rate in control mice treated with saline. When HSV-1 infected mice (recipients) received CD8+T cell fractions derived from spleens of mice treated with TJS-109 (donors), 70% of recipients survived, as compared with 0% survivors in the groups of mice treated with saline, B cell fractions, CD4+ T cell fractions or macrophage-enriched fractions prepared from the same donors. TJS-109 did not show any virucidal activities against HSV-1 or any virostatic activities on the growth of HSV-1 in Vero cells. These results suggest that TJS-109 protected mice exposed to lethal amounts of HSV-1 through the activation of CD8+ T cells. 相似文献
310.
本文着重研究了自还原性胺钨盐的性质及其氢还原,发现,将自还原与一般氢还原适当结合,可以高效率地制备比表面积大于20m~2/g的极细、超细钨粉。对自还原的本性及该类钨盐在制取极细、超细钨粉方面的应用前景进行了讨论。 相似文献