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791.
The cloning of the opioid receptors allows the investigation of receptor domains involved in the peptidic and nonpeptidic ligand interaction and activation of the opioid receptors. Receptor chimera studies and mutational analysis of the primary sequences of the opioid receptors have provided insights into the structural domains required for the ligand recognition and receptor activation. In the current review, we examine the current reports on the possible involvement of extracellular domains and transmembrane domains in the high-affinity binding of peptidic and nonpeptidic ligands to the opioid receptor. The structural requirement for the receptors' selectivity toward different ligands is discussed. The receptor domains involved in the activation and subsequent cellular regulation of the receptors' activities as determined by mutational analysis will also be discussed. Finally, the validity of the conclusions based on single amino acid mutations is examined. 相似文献
792.
793.
Metz AM Wong KC Malmström SA Browning KS 《Biochemical and biophysical research communications》1999,266(2):314-321
Clones of eukaryotic initiation factor (eIF) 4B from wheat and Arabidopsis thaliana were obtained from cDNA and genomic libraries. The exon/intron organization of the genes from wheat and A. thaliana is very similar. The deduced amino acid sequences for the wheat and Arabidopsis eIF4B proteins showed overall similarity to each other, but very little similarity to eIF4B from other eukaryotes. The recombinant form of eIF4B supports polypeptide synthesis in an in vitro translation system and reacts with antibodies to native wheat eIF4B. In contrast to mammalian eIF4B and eIF4A, the combination of wheat eIF4B and eIF4A does not stimulate RNA-dependent ATP hydrolysis activity; however, wheat eIF4B does stimulate eIF4F and eIF4A RNA-dependent ATP hydrolysis activity. Interestingly, eIF4B does not stimulate eIF(iso)4F and eIF4A hydrolysis activity. Gel filtration experiments indicate wheat eIF4B, like its mammalian counterpart, self-associates to form a homodimer. 相似文献
794.
Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes 总被引:29,自引:0,他引:29
McDermott MF Aksentijevich I Galon J McDermott EM Ogunkolade BW Centola M Mansfield E Gadina M Karenko L Pettersson T McCarthy J Frucht DM Aringer M Torosyan Y Teppo AM Wilson M Karaarslan HM Wan Y Todd I Wood G Schlimgen R Kumarajeewa TR Cooper SM Vella JP Amos CI Mulley J Quane KA Molloy MG Ranki A Powell RJ Hitman GA O'Shea JJ Kastner DL 《Cell》1999,97(1):133-144
Autosomal dominant periodic fever syndromes are characterized by unexplained episodes of fever and severe localized inflammation. In seven affected families, we found six different missense mutations of the 55 kDa tumor necrosis factor receptor (TNFR1), five of which disrupt conserved extracellular disulfide bonds. Soluble plasma TNFR1 levels in patients were approximately half normal. Leukocytes bearing a C52F mutation showed increased membrane TNFR1 and reduced receptor cleavage following stimulation. We propose that the autoinflammatory phenotype results from impaired downregulation of membrane TNFR1 and diminished shedding of potentially antagonistic soluble receptor. TNFR1-associated periodic syndromes (TRAPS) establish an important class of mutations in TNF receptors. Detailed analysis of one such mutation suggests impaired cytokine receptor clearance as a novel mechanism of disease. 相似文献
795.
Wong KK Colfen H Whilton NT Douglas T Mann S 《Journal of inorganic biochemistry》1999,76(3-4):187-195
Alkylated derivatives of the iron storage protein, ferritin, have been prepared by carbodiimide-activated coupling of long chain (C9, C12, C14) primary amines to surface carboxylic acid residues. In the case of a nonyl-derivatized protein, alkylation results in covalent modification of approximately 400 of the 520 amino acid carboxyl groups in the protein molecule. The hydrophobic proteins have a net positive charge in water and can be transferred from THF/water mixtures into dichloromethane, ethyl acetate and toluene by addition of small amounts of NaCl. Transmission electron microscopy, analytical ultracentrifugation, and polyacrylamide gel electrophoresis indicate that the hydrophobic proteins dissolve in the organic solvents as structurally intact, non-aggregated macromolecules which can be subsequently back-extracted into water. 相似文献
796.
797.
Pei Jian-Ming; Yu Xiao-Chun; Bian Jin-Song; Wong Tak-Ming 《American journal of physiology. Cell physiology》1999,277(3):C492
To study the effects of -opioid receptor stimulation onintracellular Ca2+ concentration([Ca2+]i)homeostasis during extracellular acidosis, we determined the effects of-opioid receptor stimulation on[Ca2+]iresponses during extracellular acidosis in isolated single ratventricular myocytes, by a spectrofluorometric method. U-50488H (10-30 µM), a selective -opioid receptor agonist, dosedependently decreased the electrically induced[Ca2+]itransient, which results from the influx ofCa2+ and the subsequentmobilization of Ca2+ from thesarcoplasmic reticulum (SR). U-50488H (30 µM) also increased theresting[Ca2+]iand inhibited the[Ca2+]itransient induced by caffeine, which mobilizesCa2+ from the SR, indicating thatthe effects of the -opioid receptor agonist involved mobilization ofCa2+ from its intracellular poolinto the cytoplasm. The Ca2+responses to 30 µM U-50488H were abolished by 5 µMnor-binaltorphimine, a selective -opioid receptorantagonist, indicating that the event was mediated by the -opioidreceptor. The effects of the agonist on[Ca2+]iand the electrically induced[Ca2+]itransient were significantly attenuated when the extracellular pH(pHe) was loweredto 6.8, which itself reduced intracellular pH(pHi) and increased[Ca2+]i.The inhibitory effects of U-50488H were restored during extracellular acidosis in the presence of 10 µM ethylisopropyl amiloride, a potentNa+/H+exchange blocker, or 0.2 mM Ni2+,a putativeNa+/Ca2+exchange blocker. The observations indicate that acidosismay antagonize the effects of -opioid receptor stimulation viaNa+/H+andNa+/Ca2+exchanges. When glucose at 50 mM, known to activate theNa+/H+exchange, was added, both the resting[Ca2+]iand pHi increased. Interestingly,the effects of U-50488H on [Ca2+]iand the electrically induced[Ca2+]itransient during superfusion with glucose were significantly attenuated; this mimicked the responses during extracellular acidosis. When a high-Ca2+ (3 mM) solutionwas superfused, the resting[Ca2+]iincreased; the increase was abolished by 0.2 mMNi2+, but thepHi remained unchanged. Like theresponses to superfusion with high-concentration glucose andextracellular acidosis, the responses of the[Ca2+]iand electrically induced[Ca2+]itransients to 30 µM U-50488H were also significantly attenuated. Results from the present study demonstrated for the first time thatextracellular acidosis antagonizes the effects of -opioid receptorstimulation on the mobilization ofCa2+ from SR. Activation of bothNa+/H+andNa+/Ca2+exchanges, leading to an elevation of[Ca2+]i,may be responsible for the antagonistic action of extracellular acidosis against -opioid receptor stimulation. 相似文献
798.
内源性一氧化氮在内毒素引起的肺动脉高压和肺损伤中的作用 总被引:18,自引:2,他引:16
本实验观察了家兔静脉内注入内毒素的主要成分脂多糖(LPS)后平均动脉血压(MAP)、肺动脉压(PAP)及入、出肺血NO含量的变化,并观察了静脉内预注入NO生成抑制剂Nω-硝基-L-精氨酸(L-NNA)及诱生型NO生成抑制剂氨基胍(AG)后PAP和肺损伤的变化.结果观察到:家兔LPS注入后,MAP均明显下降,LPS注入后0.5、1、1.5、2h PAP明显增高(P<0.05).LPS注入后PAP的高峰期(1h)入肺血NO含量明显降低,出肺血NO无明显变化.与对照组相比,LPS注入后3h出肺血NO含量和5h入、出肺血NO含量均明显增多.相关分析表明,兔LPS注入前和LPS注入后1h PAP与入肺血NO含量呈明显的负相关,而LPS注入后 3h和5h两者相关不明显.静脉预注入L-NNA后,LPS处理组的动物PAP明显增高,入、出肺血丙二醛(MDA)含量也明显增高,动物生存率明显降低.肺组织光镜下可见肺萎陷和小血管淤血加重,白细胞明显增加.静脉预注入AG后,LPS处理组的动物MAP在3~5h明显增高,此时PAP无明显改变,但5h时血中MDA含量明显减低,5h时与LPS组相比肺萎陷和小血管淤血减轻,白细胞也明显减少.以上结果提示,内毒素入血后较早期阶段可出现PAP的升高,此时入肺血NO的减少是参与肺动脉压增高(PAH)的机制之一.家兔内毒素进入血后较早期阶段NO对减轻内毒素引起的PAH和肺损伤起重要作用,而较晚的时期当诱生型NO合酶(iNOS)诱生后释放的NO则参与内毒素引起的肺组织炎症反应和肺损伤. 相似文献
799.
An intronic enhancer regulates splicing of the twintron of Drosophila melanogaster prospero pre-mRNA by two different spliceosomes
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We have examined the alternative splicing of the Drosophila melanogaster prospero twintron, which contains splice sites for both the U2- and U12-type spliceosome and generates two forms of mRNA, pros-L (U2-type product) and pros-S (U12-type product). We find that twintron splicing is developmentally regulated: pros-L is abundant in early embryogenesis while pros-S displays the opposite pattern. We have established a Kc cell in vitro splicing system that accurately splices a minimal pros substrate containing the twintron and have examined the sequence requirements for pros twintron splicing. Systematic deletion and mutation analysis of intron sequences established that twintron splicing requires a 46-nucleotide purine-rich element located 32 nucleotides downstream of the U2-type 5' splice site. While this element regulates both splicing pathways, its alteration showed the severest effects on the U2-type splicing pathway. Addition of an RNA competitor containing the wild-type purine-rich element to the Kc extract abolished U2-type splicing and slightly repressed U12-type splicing, suggesting that a trans-acting factor(s) binds the enhancer element to stimulate twintron splicing. Thus, we have identified an intron region critical for prospero twintron splicing as a first step towards elucidating the molecular mechanism of splicing regulation involving competition between the two kinds of spliceosomes. 相似文献
800.