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L Huang

Publications and source records attributed to L Huang.

At least 235 records · Page 13Linked to original sources
PubMed1999

alpha5 subunit in Trypanosoma brucei proteasome can self-assemble to form a cylinder of four stacked heptamer rings.

The proteasomes have a central role in catalysing protein degradation among both prokaryotes and eukaryotes. The 20 S proteasome constitutes their catalytic core. In studying the structure of Trypanosoma brucei 20 S proteasomes, we isolated by two-dimensional (2D) gel electrophoresis a 27 kDa subunit protein with an estimated pI of 4.7 and subjected it to mass spectrometric analysis. A tryptic peptide sequence from the protein was found identical with that of the rat alpha5 subunit. With the use of antiserum against T. brucei 20 S proteasomes to screen a T. b. rhodesiense lambda expression cDNA library, we obtained a cDNA clone encoding a full-length protein of 246 amino acid residues with a calculated molecular mass of 27174 Da and a pI of 4.71. It bears 50. 0% and 46.3% sequence identity with rat and yeast proteasome subunit alpha5 respectively, and matches all the peptide sequences derived from MS of the 2D gel-purified protein. The protein is thus designated the alpha5 subunit of T. brucei 20 S proteasome (TbPSA5). The recombinant protein, expressed in plasmid-transformed Escherichia coli, was found in a 27 kDa monomer form as well as polymerized forms with estimated molecular masses ranging from 190 to 800 kDa. Under the electron microscope, the most highly polymerized forms bear the appearance of cylinders of four-stacked heptamer rings with an estimated outer diameter of 14.5 nm and a length of 18 nm, which were immunoprecipitable by anti-(T. brucei 20 S proteasome) antiserum. In view of the documented self-assembly of the archaeon proteasome alpha subunit into double heptamer rings and the spontaneous assembly of the two alpha subunits from the 20 S proteasome of Rhodococcus erythropolis, the self-assembly of the T. brucei alpha subunit might reflect a common feature of proteasome biogenesis shared by prokaryotes and primitive eukaryotes such as the trypanosomes but apparently lost among the higher forms of eukaryote such as the yeast and the mammals.

Amino Acid Sequence↗
PubMed1999

Mechanism of ubiquinol oxidation by the bc(1) complex: role of the iron sulfur protein and its mobility.

Native structures of ubihydroquinone:cytochrome c oxidoreductase (bc(1) complex) from different sources, and structures with inhibitors in place, show a 16-22 A displacement of the [2Fe-2S] cluster and the position of the C-terminal extrinsic domain of the iron sulfur protein. None of the structures shows a static configuration that would allow catalysis of all partial reactions of quinol oxidation. We have suggested that the different conformations reflect a movement of the subunit necessary for catalysis. The displacement from an interface with cytochrome c(1) in native crystals to an interface with cytochrome b is induced by stigmatellin or 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT) and involves ligand formation between His-161 of the [2Fe-2S] binding cluster and the inhibitor. The movement is a rotational displacement, so that the same conserved docking surface on the iron sulfur protein interacts with cytochrome c(1) and with cytochrome b. The mobile extrinsic domain retains essentially the same tertiary structure, and the anchoring N-terminal tail remains in the same position. The movement occurs through an extension of a helical segment in the short linking span. We report details of the protein structure for the two main configurations in the chicken heart mitochondrial complex and discuss insights into mechanism provided by the structures and by mutant strains in which the docking at the cytochrome b interface is impaired. The movement of the iron sulfur protein represents a novel mechanism of electron transfer, in which a tethered mobile head allows electron transfer through a distance without the entropic loss from free diffusion.

Amino Acid Sequence↗
PubMed1999

Structural and functional characterizations of the proteasome-activating protein PA26 from Trypanosoma brucei.

The activated 20 S proteasome, which has been found only in mammalian cells, is composed of two heptamer rings of an activator protein on each end of the 20 S proteasome and is inducible by interferon-gamma. A 20 S proteasome has been recently identified in a protozoan pathogen Trypanosoma brucei, but there has been no experimental evidence yet for the presence of a 26 S proteasome. Instead, an activated form of 20 S proteasome was isolated from this organism, which has significantly enhanced peptidase activities. It consists of an additional activator protein with an estimated molecular mass of 26 kDa (PA26) (To, W. Y., and Wang, C. C. (1997) FEBS Lett. 404, 253-262). The profile and sequences of tryptic peptides from PA26 were determined by mass spectrometry; no matches were found in the data base. The peptide sequences were used in reverse transcriptase-polymerase chain reaction to isolate a full-length cDNA clone encoding PA26. The protein sequence thus derived from it indicates little sequence identity with those of mammalian activator proteins PA28 alpha, beta, or gamma. There is only a single copy of PA26 gene in T. brucei. Purified recombinant PA26 polymerizes spontaneously to form heptamer ring with an outer diameter of 8.5 nm. The ring binds and activates 20 S proteasomes from T. brucei as well as rat, whereas human PA28alpha can neither bind nor activate T. brucei 20 S proteasome. The former is thus apparently more ubiquitous than PA28 in its capability of binding to and activating 20 S proteasomes. Its presence in T. brucei may also suggest a more ancient origin of proteasome activator proteins and a much wider involvement in protein degradation among other eukaryotic organisms than was originally envisaged.

Amino Acid Sequence↗
PubMed1999

Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade.

The E6AP ubiquitin-protein ligase (E3) mediates the human papillomavirus-induced degradation of the p53 tumor suppressor in cervical cancer and is mutated in Angelman syndrome, a neurological disorder. The crystal structure of the catalytic hect domain of E6AP reveals a bilobal structure with a broad catalytic cleft at the junction of the two lobes. The cleft consists of conserved residues whose mutation interferes with ubiquitin-thioester bond formation and is the site of Angelman syndrome mutations. The crystal structure of the E6AP hect domain bound to the UbcH7 ubiquitin-conjugating enzyme (E2) reveals the determinants of E2-E3 specificity and provides insights into the transfer of ubiquitin from the E2 to the E3.

Amino Acid Sequence↗
PubMed1999

Subcellular trafficking of the cytoplasmic expression system.

Cationic liposomes have provided many advantages over viral vector formulations; however, the problem of inefficient gene expression remains. This is due in part to the nuclear membrane, which limits DNA entry into the nucleus. Cytoplasmic expression systems using T7 RNA polymerase have been developed to express genes in the cytoplasm and avoid the need for nuclear import of DNA. Although these systems show improved transgene expression, little is known about how they function in transfected cells. Direct comparisons between a cytoplasmic and nuclear expression system were carried out with a 293 cell line stably expressing T7 RNA polymerase. A formulation for optimal reporter gene expression was developed and used in conjunction with a variety of subcellular trafficking inhibitors to study the process of DNA endocytosis. Transfected cells were also studied at different stages of the cell cycle to determine the dependence of each system on mitosis. These results showed that cytoplasmic and nuclear expression systems utilize similar endocytosis pathways to the point of endosomal release. Once DNA is released into the cytoplasm, the cytoplasmic expression system shows immediate expression that is proportional to the amount of DNA released. In contrast, DNA targeted for nuclear expression requires additional time for nuclear entry. The level of nuclear expression is also restricted by the limited amount of DNA that is imported into the nucleus. Finally, mitosis is required for effective nuclear expression but not for cytoplasmic expression. Therefore, the cytoplasmic expression system has considerable advantages over traditional nuclear expression systems and may be an effective method for transfecting nondividing cells. Efficient expression of genes delivered by nonviral vectors is hindered owing to poor nuclear transport of plasmid DNA. A potential solution to this problem would be to use a cytoplasmic expression system. Previous studies have shown that this method produces enhanced gene expression when compared with traditional nuclear expression systems; however, the actual mechanisms by which the cytoplasmic expression system works remains unknown. This article focuses on a direct comparison between cytoplasmic and nuclear expression in terms of optimal DNA delivery formulations, intracellular trafficking of DNA, and cell cycle dependence. These results indicate that the cytoplasmic expression system has two primary advantages over nuclear expression in that it does not rely on nuclear DNA transport or mitosis for efficient expression.

Anti-Bacterial Agents↗
PubMed1999

[Evaluation on the effect of reducing body fat by biological impedance assay].

Forty-six female workers (26-55 year-old) were divided into 3 groups and engaged in 3 energy restricted dietary program respectively for 3 weeks. The change of weight, skinfold thickness and the body fat measured by biological impedance (BIA) was observed. The results showed that the effectiveness of restriction on dietary energy intake under the assist of reducing body fat supplementary foods was better. Setting an interval period on usual low calorie diet without supplements between the strictly energy restricted period was more suitable for strengthening the effectiveness on reducing body fat.

Adult↗
PubMed1999

Effect of Polyvinyl Pyrrolidone on the Thermal Phase Transition of 1,2 Dipalmitoyl-sn-glycero-3-phosphocholine Bilayer.

The purpose of this study was to investigate the interaction of polyvinyl pyrrolidone (PVP) with phospholipid bilayers in an effort to add a new dimension to our understanding of polymer interaction with lipids. For the preparation of lipid-polymer dispersions, measured amounts of DPPC (1,2 dipalmitoyl-sn-glycero-3-phosphocholine) and PVP were mixed in chloroform. After complete elimination of organic solvent, the dry mixtures were hydrated at 50-55 degrees C. Interactions between DPPC and PVP were assessed by differential scanning calorimetry (DSC) and photon correlation spectroscopy (PS). Separation of liposomes and micelles was performed by centrifugation. Liquid scintillation counting and a UV spectrophotometer were used for their analysis. PVP added as dry powder or added as aqueous solution to dry lipid or preformed liposomes failed to interact. Only PVP previously dissolved in chloroform interacted with DPPC. The DPPC main phase transition moved to lower temperatures with increasing PVP concentrations. This reduction of the phase transition temperature was accompanied by an increase of the DPPC phase transition enthalpy. Analysis of solubilization indicated that the amount of PVP present in the bilayer is dependent on the PVP bulk concentration. The data suggest interaction of PVP previously dissolved in chloroform with the acyl chains of the phospholipid deep into the bilayer. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Effect of Grafted Amphiphilic PVP-Palmityl Polymers on the Thermotropic Phase Behavior of 1,2 Dipalmitoyl- sn-glycero-3-phosphocholine Bilayer.

To better understand how grafted polymers interact with liposome membrane, a comparative study was conducted to investigate the influence of different chain length polyvinyl pyrrolidone-palmityl (PVP-p) conjugates on the thermotropic phase behavior of 1,2 dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) bilayer. Lipid-polymer dispersions were prepared by mixing DPPC and variable concentrations of PVP-p conjugates in chloroform. Hydration of lipids was performed at 50-55 degrees C after complete elimination of the organic solvent. Differential scanning calorimetry (DSC) was used to determine lipid miscibility and bilayer-polymer interactions. Particle size was determined by photon correlation spectroscopy. Increasing concentrations of 6 kDa PVP-p caused a shift of the main phase transition of DPPC at lower temperatures. At 9.1 mol% the DPPC phase pretransition (T(p)) is abolished. At 16.7 mol%, differential scanning calorimetry showed an endothermic phase transition at 24.9 degrees C. The enthalpy of this transition was twice as high compared to the main phase transition enthalpy of pure DPPC. Inclusion of more than 20 mol% of 6 kDa PVP-p resulted in a complete bilayer micellization. Qualitatively similar to the 6 kDa were the results obtained with the 12 kDa PVP-p conjugate. Increasing concentrations of 25 kDa PVP-p from 1 to 13 mol% resulted in a decrease of the main DPPC phase transition temperature. At 13 mol% the new molecular self-assembled structure as previously identified with the lower MW PVP-p conjugates also showed up at the DSC thermogram. However, in sharp contrast to the lower MW PVP-p conjugates, increasing the 25 kDa PVP-p content did not result in bilayer disruption; rather, it resulted in a bilayer stabilization. The consequences of the hydrophobically modified PVP interaction with the bilayer are considered negative with respect to the long-circulating properties of liposomes in the blood. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

The inhibitory role of CpG immunostimulatory motifs in cationic lipid vector-mediated transgene expression in vivo.

We have previously reported that intravenous administration of cationic lipid-protamine-DNA complexes (LPD) induces production of large quantities of proinflammatory cytokines that are toxic and cause inhibition of transgene expression. Cytokine induction appears to be mediated by the unmethylated CpG sequences since methylation of plasmid DNA significantly decreases the cytokine levels. In this study, the inhibitory role of CpG in lipid-mediated gene transfer was further investigated using chemically well-defined, CpG-containing oligodeoxynucleotides (ODNs). Injection (intravenous) of ODNs formulated in LPD into mice triggered production of proinflammatory cytokines including interferon gamma and TNF-alpha. The potency of CpG-containing ODNs in cytokine induction was affected by its flanking sequences and was significantly reduced when CpG was methylated. Preinjection of ODN-containing LPD led to inhibition of transgene expression in lungs after a subsequent injection of LPD containing plasmid expression vector with luciferase gene. The degree of inhibition correlated with the levels of ODN-triggered cytokines. Finally, intraperitoneal injection of dexamethasone suppressed LPD-induced cytokine production, and led to significantly higher levels of transgene expression on both first and second injection. These studies suggest that mutation of potent CpG motifs in plasmid DNA together with the use of immune suppression agent may represent an effective approach to improve cationic lipid-mediated gene transfer to the lung.

Animals↗
PubMed1999

Identification and isolation of three proteasome subunits and their encoding genes from Trypanosoma brucei.

We have determined peptide sequences of three Trypanosoma brucei proteasome subunit proteins by mass spectrometry of tryptic digests of the proteins purified by two-dimensional (2-D) polyacrylamide gel electrophoresis. Three genes identified by the sequence of their cDNA encode the peptides identified in these three proteins. The three proteins predicted from the gene sequences have significant similarity to other known proteasome subunits and represent an alpha6 type subunit (TbPSA6), and two beta-type subunits belonging to the beta1-type (TbPSB1) and beta2 type (TbPSB2). The sequences of both beta-subunits predict formation of catalytically active subunits through proteolytic processing. The prediction is supported by the presence in each of the two beta-subunits of a tryptic peptide that has the correctly processed N-terminus that creates the threonine nucleophile of the mature protein. This peptide cannot be generated by trypsin because of the required cleavage of a glycine-threonine bond. It is thus likely that there are at least two catalytically active beta-subunits, TbPSB1 and TbPSB2, present in the mature 20S proteasome from T. brucei.

Amino Acid Sequence↗
PubMed1999

A genetically modified recombinant tumor necrosis factor-alpha conjugated to the distal terminals of liposomal surface grafted polyethyleneglycol chains.

A genetically modified recombinant tumor necrosis factor (TNF)-alpha (rKRKTNF) was conjugated to the terminal carboxyl groups of liposome grafted polyethyleneglycol (PEG) chains. The long-circulating liposomes were composed of egg phosphatidylcholine, cholesterol (chol) and 7% carboxyl PEG-phosphatidylethanolamine. The conjugation efficiency of the genetically modified rKRKTNF under the conditions described in the text was approximately 55%. The biological activity of liposomal rKRKTNF, as tested with an in vitro cytotoxicity assay was reduced compared to the free, unconjugated rKRKTNF. In vivo biodistribution studies showed that conjugation of as little as 0. 13% of the grafted PEG chains resulted in a rapid elimination of the formulation from the blood stream. It is speculated that both non-selective conjugate chemistry and inherent recognition of the TNF by the components of the reticuloendothelial system (RES) are responsible for the short blood half life of the rKRKTNF-PEG-liposomes. The result suggest that conjugating a rapidly clearing recombinant cytokine to long-circulating liposomes provides little advantage in modifying the pharmacokinetic parameters of the cytokine.

Animals↗
PubMed1999

Neurotrophins and Trk receptors in human pancreatic ductal adenocarcinoma: expression patterns and effects on in vitro invasive behavior.

The aggressive and highly metastatic behavior observed in pancreatic ductal adenocarcinoma (PDAC) may be due to autocrine and/or paracrine interactions (tumor/stromal) involving altered expression of peptide growth factors and their corresponding receptors. The neurotrophin (NT) growth factor family and their cognate receptors have been demonstrated to play a role in the invasiveness, chemotactic behavior and tumor cell survival of both neuronal and non-neuronal cancers. We hypothesized that aberrant expression of the NTs and/or the Trk receptors may contribute to the malignant phenotype of PDAC, specifically tumor cell invasiveness, through autocrine and/or paracrine interactions. In this study, we examined the expression of NTs, Trks and p75NGFR by immunohistochemical and in situ hybridization analyses in both normal (n=14) and neoplastic pancreas (n=47) and PDAC-derived cell lines (n=6). Further, we evaluated the effects of various NTs on the in vitro invasive and chemotactic behavior on 6 human PDAC-derived cell lines in a modified Boyden chamber assay. Brain-derived nerve growth factor (BDNF), NT-3, NT-4/5 and Trks A, B and C exhibited diffuse cytoplasmic and membranous immunostaining patterns in both the ducts and the acini of the exocrine pancreas and the islets of the endocrine pancreas of both normal and PDAC specimens. NT expression was primarily within the stromal compartment of the tumor, while Trk expression was weak or absent. We observed a 68%, 64% and 66% increase in the expression of Trks A, B and C, respectively, in the ductal elements of the PDAC samples examined compared with the normal adjacent tissue. Invasiveness of 4 of 6 PDAC cell lines was significantly inhibited (p<0.05) when the cells were incubated with 100 ng/ml NT. However, when select cell lines were incubated with lower concentrations of NT-3 and BDNF (0, 1, 5, 25 and 50 ng/ml), invasiveness was significantly stimulated (p<0.05) through the Matrigel matrix. Collectively, our data suggest the possibility that paracrine and/or autocrine NT-Trk interactions may influence the phenotype (possibly the invasive behavior) of PDAC.

3T3 Cells↗
PubMed1999

Biosynthesis of 3-acetyldeoxynivalenol and sambucinol. Identification of the two oxygenation steps after trichodiene.

The first two oxygenation steps post-trichodiene in the biosyntheses of the trichothecenes 3-acetyldeoxynivalenol and sambucinol were investigated. The plausible intermediates 2-hydroxytrichodiene (2alpha- and 2beta-) and 12,13-epoxytrichodiene and the dioxygenated compounds 12,13-epoxy-9,10-trichoene-2-ol (2alpha- and 2beta-) were prepared specifically labeled with stable isotopes. They were then fed separately and/or together to Fusarium culmorum cultures, and the derived trichothecenes were isolated, purified, and analyzed. The stable isotopes enable easy localization of the labels in the products by 2H NMR, 13C NMR, and mass spectrometry. We found that 2alpha-hydroxytrichodiene is the first oxygenated step in the biosynthesis of both 3-acetyldeoxynivalenol and sambucinol. The stereoisomer 2beta-hydroxytrichodiene and 12,13-epoxytrichodiene are not biosynthetic intermediates and have not been isolated as metabolites. We also demonstrated that the dioxygenated 12, 13-epoxy-9,10-trichoene-2alpha-ol is a biosynthetic precursor to trichothecenes as had been suggested in a preliminary work. Its stereoisomer was not found in the pathway. A further confirmation of our results was the isolation of both oxygenated trichodiene derivatives 2alpha-hydroxytrichodiene and 12,13-epoxy-9, 10-trichoene-2alpha-ol as natural metabolites in F. culmorum cultures.

Cyclohexenes↗
PubMed1999

Replacement of threonine 558, a critical site of phosphorylation of moesin in vivo, with aspartate activates F-actin binding of moesin. Regulation by conformational change.

Point and deletion mutants of moesin were examined for F-actin binding by blot overlay and co-sedimentation, and for intra- and intermolecular interactions with N- and C-terminal domains with yeast two-hybrid and in vitro binding assays. Wild-type moesin molecules interact poorly with F-actin and each other, and bind neither C- nor N-terminal fragments. Interaction with F-actin is strongly enhanced by replacement of Thr558 with aspartate (T558D), by deletion of 11 N-terminal residues (DelN11), by deletion of the entire N-terminal membrane-binding domain of both wild type and T558D mutant molecules, and by exposure to phosphatidylinositol 4, 5-diphosphate. Activation of F-actin binding is accompanied by changes in inter- and intramolecular domain interactions. The T558D mutation renders moesin capable of binding wild type but not mutated (T558D) C-terminal or wild type N-terminal fragments. The interaction between the latter two is prevented. DelN11 truncation enables binding of wild type N and C domain fragments. These changes suggest that the T558D mutation, mimicking phosphorylation of Thr558, promotes F-actin binding by disruption of interdomain interactions between N and C domains and exposure of the high affinity F-actin binding site in the C-terminal domain. Oscillation between activated and resting state could thus provide the structural basis for transient interactions between moesin and the actin cytoskeleton in protruding and retracting microextensions.

Actins↗
PubMed1999

RB-mediated suppression of spontaneous multiple neuroendocrine neoplasia and lung metastases in Rb+/- mice.

Alterations in pathways mediated by retinoblastoma susceptibility gene (RB) product are among the most common in human cancer. Mice with a single copy of the Rb gene are shown to develop a syndrome of multiple neuroendocrine neoplasia. The earliest Rb-deficient atypical cells were identified in the intermediate and anterior lobes of the pituitary, the thyroid and parathyroid glands, and the adrenal medulla within the first 3 months of postnatal development. These cells form gross tumors with various degrees of malignancy by postnatal day 350. By age of 380 days, 84% of Rb+/- mice exhibited lung metastases from C-cell thyroid carcinomas. Expression of a human RB transgene in the Rb+/- mice suppressed carcinogenesis in all tissues studied. Of particular clinical relevance, the frequency of lung metastases also was reduced to 12% in Rb+/- mice by repeated i.v. administration of lipid-entrapped, polycation-condensed RB complementary DNA. Thus, in spite of long latency periods during which secondary alterations can accumulate, the initial loss of Rb function remains essential for tumor progression in multiple types of neuroendocrine cells. Restoration of RB function in humans may prove an effective general approach to the treatment of RB-deficient disseminated tumors.

Animals↗
PubMed1999

Nitric oxide-generated P420 nitric oxide synthase: characterization and roles for tetrahydrobiopterin and substrate in protecting against or reversing the P420 conversion.

The neuronal NO synthase (nNOS) heme binds self-generated NO, and this negatively regulates NO synthesis. Here we utilized the nNOS oxygenase domain and full-length nNOS along with various spectroscopic methods to (1) study formation of the six-coordinate ferrous NO complex and its conversion to a five-coordinate NO complex and (2) investigate the spectral and catalytic properties of the five-coordinate NO complex following its air oxidation to a ferric enzyme. NO bound quickly to ferrous nNOS oxygenase to form a six-coordinate NO complex (kon and koff values of 1.25 x 10(-)3 mM-1 s-1 and 128 s-1 at 10 degreesC, respectively) that was stable in the presence of L-arginine or tetrahydrobiopterin (BH4) but was converted to a five-coordinate NO complex in a biphasic process (k = 0.1 and 0.01 s-1 at 10 degreesC) in the absence of these molecules. Air oxidation of the ferrous six-coordinate NO complex generated an enzyme with full activity and ferrous-CO Soret absorbance at 444 nm. In contrast, oxidation of the five-coordinate NO complex generated an inactive dimer with ferrous-CO Soret absorbance at 420 nm, indicating nNOS was converted to a ferric P420 form. Incubation of ferric P420 nNOS with BH4 alone or BH4 and L-arginine resulted in time-dependent reactivation of catalysis and associated recovery of P450 character. Thus, nNOS is a heme-thiolate protein that can undergo a reversible P450-P420 conversion. BH4 has important roles in preventing P420 formation during NO synthesis, and in rescuing P420 nNOS.

Air↗
PubMed1999

Induction of long-lasting depression by (+)-alpha-methyl-4-carboxyphenylglycine and other group II mGlu receptor ligands in the dentate gyrus of the hippocampus in vitro.

Application of several well characterized group II mGlu receptor ligands was found to induce a long-lasting depression of synaptic transmission in the medial perforant path of the dentate gyrus. These ligands were N-acetylaspartylglutamate (NAAG), which is a dipeptide located in the brain and possibly functioning as a neurotransmitter, two agents widely used previously as mGluR antagonists, (+)-alpha-methyl-4-carboxyphenylglycine (MCPG), and (S)-alpha-ethylglutamate (EGLU), and the well characterized group II mGluR agonist (2S,1R,2R,3R)-2-(2S,1'R,2'R,3'R)-2(2'3'-dicarboxycyclopropyl)glyci ne (DCG-IV). It is postulated that all these ligands induced the long-lasting depression by an agonist/partial agonist action at group II mGlu receptor. The long-lasting depression induced by the ligands showed mutual occlusion with low frequency stimulation-induced long-term depression, demonstrating common induction or maintenance mechanisms. The induction of the long-lasting depression by the mGlu receptor ligands are suggested to occur postsynaptically as the induction was not associated with a change in paired pulse depression of excitatory postsynaptic potentials (EPSPs).

Animals↗