Re-Evaluation of Nicotinic Acetylcholine Receptors in Rat Brain by a Tissue-Segment Binding Assay

Nicotinic acetylcholine receptors (nAChRs) of the cerebral cortex and cerebellum of rats were evaluated by a radioligand binding assay, employing tissue segments, or homogenates as materials. [3H]-epibatidine specifically bound to nAChRs in rat cortex or cerebellum, but the dissociation constants for [3H]-epibatidine differed between segments and homogenates (187 pM for segments and 42 pM for homogenates in the cortex and 160 pM for segments and 84 pM for homogenates in the cerebellum). The abundance of total nAChRs was approximately 310 fmol/mg protein in the segments of cortex and 170 fmol/mg protein in the segments of cerebellum, which were significantly higher than those estimated in the homogenates (115 fmol/mg protein in the homogenates of the cortex and 76 fmol/mg protein in the homogenates of the cerebellum). Most of the [3H]-epibatidine binding sites in the cortex segments (approximately 70% of the population) showed high affinity for nicotine (pKi = 7.9), dihydro-β-erythroidine, and cytisine, but the binding sites in the cerebellum segments had slightly lower affinity for nicotine (pKi = 7.1). An upregulation of nAChRs by chronic administration of nicotine was observed in the cortex segments but not in the cerebellum segments with [3H]-epibatidine as a ligand. The upregulation in the cortex was caused by a specific increase in the high-affinity sites for nicotine (probably α4β2). The present study shows that the native environment of nAChRs is important for a precise quantitative as well as qualitative estimation of nAChRs in rat brain

AMPA型グルタミン酸受容体GluR2サブユニットのN-エチルマレイミド感受性融合タンパク質(NSF)による活性調節に関する研究

京都大学0048新制・課程博士博士(医学)甲第8277号医博第2233号新制||医||737(附属図書館)UT51-2000-F181京都大学大学院医学研究科分子医学系専攻(主査)教授 川口 三郎, 教授 大森 治紀, 教授 中西 重忠学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

The PDZ Proteins PICK1, GRIP, and Syntenin Bind Multiple Glutamate Receptor Subtypes

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GISP: a novel brain-specific protein that promotes surface expression and function of GABABreceptors

Synaptic transmission depends on the regulated surface expression of neurotransmitter receptors, but many of the cellular processes required to achieve this remain poorly understood. To better define specific mechanisms for the GABA(B) receptor (GABA(B)R) trafficking, we screened for proteins that bind to the carboxy-terminus of the GABA(B1) subunit. We report the identification and characterization of a novel 130-kDa protein, GPCR interacting scaffolding protein (GISP), that interacts directly with the GABA(B1) subunit via a coiled-coil domain. GISP co-fractionates with GABA(B)R and with the postsynaptic density and co-immunoprecipitates with GABA(B1) and GABA(B2) from rat brain. In cultured hippocampal neurons, GISP displays a punctate dendritic distribution and has an overlapping localization with GABA(B)Rs. When co-expressed with GABA(B)Rs in human embryonic kidney cells, GISP promotes GABA(B)R surface expression and enhances both baclofen-evoked extracellular signal-regulated kinase (ERK) phosphorylation and G-protein inwardly rectifying potassium channel (GIRK) currents. These results suggest that GISP is involved in the forward trafficking and stabilization of functional GABA(B)Rs

Radiological impact of TEPCO\u27s Fukushima Dai-ichi Nuclear Power Plant accident on invertebrates in the coastal benthic food web

Radioactive cesium (134Cs and 137Cs) concentrations in invertebrates of benthic food web (10 taxonomic classes with 46 identified families) collected from wide areas off Fukushima Prefecture (3e500 m depth) were inspected from July 2011, four months after the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident, to August 2013 to elucidate time-series trends among taxa and areas. Cesium-137 was detected in seven classes (77% of 592 specimens). Higher 137Cs concentrations within detected data were often found in areas near or south of the FDNPP, which is consistent with the reported spatial distribution of 137Cs concentrations in highly contaminated seawater and sediments after the FDNPP accident. Overall 137Cs concentrations in invertebrates, the maxima of which (290 Bq kg␣1-wet in the sea urchin Glyp- tocidaris crenularis) were lower than in many demersal fishes, had decreased exponentially with time, and exhibited taxon-specific decreasing trends. Concentrations in Bivalvia and Gastropoda decreased clearly with respective ecological half-lives of 188 d and 102 d. In contrast, decreasing trends in Mala- costraca and Polychaeta were more gradual, with longer respective ecological half-lives of 208 d and 487 d. Echinoidea showed no consistent trend, presumably because of effects of contaminated sediments taken into their digestive tract. Comparison of 137Cs concentrations in the invertebrates and those in seawater and sediments suggest that contaminated sediments are the major source of continuing contamination in benthic invertebrates, especially in Malacostraca and Polychaeta