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  • 1
    Publication Date: 2011-07-06
    Description: The adult stem cell marker Lgr5 and its relative Lgr4 are often co-expressed in Wnt-driven proliferative compartments. We find that conditional deletion of both genes in the mouse gut impairs Wnt target gene expression and results in the rapid demise of intestinal crypts, thus phenocopying Wnt pathway inhibition. Mass spectrometry demonstrates that Lgr4 and Lgr5 associate with the Frizzled/Lrp Wnt receptor complex. Each of the four R-spondins, secreted Wnt pathway agonists, can bind to Lgr4, -5 and -6. In HEK293 cells, RSPO1 enhances canonical WNT signals initiated by WNT3A. Removal of LGR4 does not affect WNT3A signalling, but abrogates the RSPO1-mediated signal enhancement, a phenomenon rescued by re-expression of LGR4, -5 or -6. Genetic deletion of Lgr4/5 in mouse intestinal crypt cultures phenocopies withdrawal of Rspo1 and can be rescued by Wnt pathway activation. Lgr5 homologues are facultative Wnt receptor components that mediate Wnt signal enhancement by soluble R-spondin proteins. These results will guide future studies towards the application of R-spondins for regenerative purposes of tissues expressing Lgr5 homologues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Lau, Wim -- Barker, Nick -- Low, Teck Y -- Koo, Bon-Kyoung -- Li, Vivian S W -- Teunissen, Hans -- Kujala, Pekka -- Haegebarth, Andrea -- Peters, Peter J -- van de Wetering, Marc -- Stange, Daniel E -- van Es, Johan E -- Guardavaccaro, Daniele -- Schasfoort, Richard B M -- Mohri, Yasuaki -- Nishimori, Katsuhiko -- Mohammed, Shabaz -- Heck, Albert J R -- Clevers, Hans -- England -- Nature. 2011 Jul 4;476(7360):293-7. doi: 10.1038/nature10337.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Hubrecht Institute and University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21727895" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/metabolism ; Animals ; Cells, Cultured ; Epithelial Cells/cytology/metabolism ; Frizzled Receptors/metabolism ; Gene Deletion ; HEK293 Cells ; Humans ; Mice ; Protein Binding ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled/chemistry/deficiency/genetics/*metabolism ; Regeneration ; *Signal Transduction/genetics ; Thrombospondins/*metabolism ; Wnt Proteins/genetics/*metabolism ; Wnt3 Protein ; Wnt3A Protein
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1996-02-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Levy, J A -- Ramachandran, B -- Barker, E -- Guthrie, J -- Elbeik, T -- New York, N.Y. -- Science. 1996 Feb 2;271(5249):670-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8571134" target="_blank"〉PubMed〈/a〉
    Keywords: Antiviral Agents/pharmacology/therapeutic use ; *CD4 Lymphocyte Count ; Cells, Cultured ; HIV Infections/drug therapy/immunology/*virology ; HIV-1/*physiology ; Humans ; Leukocytes, Mononuclear/*virology ; Lymphocyte Count ; T-Lymphocytes/*virology ; Tumor Cells, Cultured ; Viremia/virology ; Virus Replication ; Zidovudine/pharmacology/therapeutic use
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1996-11-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mackewicz, C E -- Barker, E -- Levy, J A -- New York, N.Y. -- Science. 1996 Nov 22;274(5291):1393-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8966605" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies/immunology ; Antiviral Agents/immunology/pharmacology/*physiology ; CD4-Positive T-Lymphocytes/*virology ; CD8-Positive T-Lymphocytes/*immunology ; Cells, Cultured ; Chemokine CCL4 ; Chemokine CCL5/immunology/pharmacology/physiology ; Chemokines/immunology/pharmacology/*physiology ; HIV Infections/virology ; HIV Long Terminal Repeat ; HIV-1/genetics/*physiology ; Humans ; Macrophage Inflammatory Proteins/immunology/pharmacology/physiology ; Neutralization Tests ; Virus Replication
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 1978-03-31
    Description: Mouse spinal neurons grown in tissue culture were used to study the electrophysiological pharmacology of the opiate peptide leucine-enkephalin. Enkephalin depressed glutamate-evoked responses in a noncompetitive manner independent of any other effects on membrane properties. The results demonstrate a neuromodulatory action of opiate peptide functionally distinct from the conventional neurotransmitter class of operation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barker, J L -- Neale, J H -- Smith, T G Jr -- Macdonald, R L -- New York, N.Y. -- Science. 1978 Mar 31;199(4336):1451-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/204016" target="_blank"〉PubMed〈/a〉
    Keywords: Cells, Cultured ; Endorphins/*pharmacology ; Enkephalins/antagonists & inhibitors/*pharmacology ; Excitatory Amino Acid Antagonists ; Glutamates/*pharmacology ; Iontophoresis ; Naloxone/pharmacology ; Neurons/*drug effects ; Spinal Cord ; Synapses/*drug effects ; Synaptic Transmission/*drug effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 1978-05-19
    Description: Barbiturate anesthetics, but not anticonvulsants, abolish the spontaneous activity of cultured spinal cord neurons; directly increase membrane conductance, an effect which is suppressed by the gamma-aminobutyric acid (GABA) antagonists picrotoxin and penicillin; and are more potent than anticonvulsants in augmenting GABA and depressing glutamate responses. Barbiturate anticonvulsants abolish picrotoxin-induced convulsive activity. These results indicate qualitative and quantitative differences between anesthetic and anticonvulsant barbiturates, which may explain their different clinical effects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Macdonald, R L -- Barker, J L -- New York, N.Y. -- Science. 1978 May 19;200(4343):775-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/205953" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/drug effects ; Cells, Cultured ; Electric Conductivity ; Glutamates/pharmacology ; Membrane Potentials/drug effects ; Neurons/*drug effects ; Pentobarbital/*pharmacology ; Phenobarbital/*pharmacology ; Picrotoxin/pharmacology ; Receptors, Neurotransmitter/drug effects ; gamma-Aminobutyric Acid/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 1979-08-17
    Description: Mouse spinal neurons grown in tissue culture were used to study the membrane effects of the benzodiazepine flurazepam and the naturally occurring purine nucleoside inosine, which competes for benzodiazepine receptor sites in the central nervous system. Application of inosine elicited two types of transmitter-like membrane effects: a rapidly desensitizing excitatory response and a nondesensitizing inhibitory response. Flurazepam produced a similar excitatory response which showed cross-desensitization with the purine excitation. Flurazepam also blocked the inhibitory inosine response. The results provide electrophysiological evidence that an endogenous purine can activate two different conductances on spinal neurons and that flurazepam can activate one of the conductances and antagonize the other.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉MacDonald, J F -- Barker, J L -- Paul, S M -- Marangos, P J -- Skolnick, P -- New York, N.Y. -- Science. 1979 Aug 17;205(4407):715-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/37602" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Benzodiazepines/*metabolism ; Cells, Cultured ; Electric Conductivity ; Flurazepam/antagonists & inhibitors ; Inosine/*metabolism/pharmacology ; Ligands ; Mice ; Neurotransmitter Agents/metabolism ; Receptors, Drug/*metabolism ; Receptors, Neurotransmitter/metabolism ; Spinal Cord/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 1979-09-28
    Description: Mouse spinal neurons grown in tissue culture were used to examine the membrane mechanisms of action of the peptide substance P. Two functionally distinct actions were observed, one being a rapidly desensitizing excitation, and the other being a dose-dependent, reversible depression of excitatory responses to the putative amino acid neurotransmitter glutamate. These effects on excitability suggest that substance P may play more than one role in intercellular communication in the nervous system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vincent, J D -- Barker, J L -- New York, N.Y. -- Science. 1979 Sep 28;205(4413):1409-12.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/224464" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Communication ; Cells, Cultured ; Electric Conductivity ; Excitatory Amino Acid Antagonists ; Glutamates/pharmacology ; Membrane Potentials ; Mice ; Neural Inhibition ; Spinal Cord/cytology/*physiology ; Substance P/*physiology ; Synaptic Transmission
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1980-07-25
    Description: Intracellular recordings from voltage-clamped mouse spinal neurons in tissue culture were used to study the membrane mechanisms underlying inhibitory responses to gamma-aminobutyric acid and the (-) isomer of pentobarbital. Fluctuation analysis suggested that both substances activated ion channels in the membranes. However, the channels activated by pentobarbital remained open five times longer than those activated by gamma-aminobutyric acid.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mathers, D A -- Barker, J L -- New York, N.Y. -- Science. 1980 Jul 25;209(4455):507-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6248961" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/drug effects/physiology ; Cells, Cultured ; Ion Channels/drug effects/*physiology ; Membrane Potentials/drug effects ; Mice ; Neurons/drug effects/*physiology ; Pentobarbital/*pharmacology ; Spinal Cord/*physiology ; gamma-Aminobutyric Acid/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 1978-08-04
    Description: Neuronal cells, axons, and terminals containing immunoreactive enkephalin have been visualized in cultures of dissociated fetal spinal cord. These cultures may provide a valuable system in which to explore the effects of chronic drug treatment on the physiology of enkephalin-containing cells and their interactions with other cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neale, J H -- Barker, J L -- Uhl, G R -- Snyder, S H -- New York, N.Y. -- Science. 1978 Aug 4;201(4354):467-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/351811" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/metabolism ; Cells, Cultured ; Cytoplasm/metabolism ; Endorphins/*metabolism ; Enkephalins/*metabolism ; Fluorescent Antibody Technique ; Ganglia, Spinal/metabolism ; Mice ; Neurons/*metabolism ; Spinal Cord/cytology/embryology/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 1980-05-30
    Description: The cellular mechanisms underlying picrotoxin-induced convulsive activity were studied by using mouse spinal neurons growing in tissue culture. Picrotoxin-induced convulsive activity in most but not all of the cells studied. The activity could be inverted by polarizing to positive potentials and eliminated either by decreasing the ratio of calcium to magnesium or by applying tetrodotoxin. When applied locally to individual cells, picrotoxin lowered spike threshold and induced spontaneous firing in some but not all cells tested. The results suggest that picrotoxin-induced convulsive activity involves rapidly summating synaptic activity which may be evoked by high-frequency repetitive firing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barker, J L -- MacDonald, J F -- New York, N.Y. -- Science. 1980 May 30;208(4447):1054-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7375918" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/drug effects ; Animals ; Calcium/pharmacology ; Cells, Cultured ; Magnesium/pharmacology ; Membrane Potentials/drug effects ; Mice ; Picrotoxin/*pharmacology ; Seizures/*chemically induced ; Spinal Cord/*drug effects/physiology ; Synapses/*drug effects
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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