Source:http://linkedlifedata.com/resource/pubmed/id/15627497
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2005-1-3
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pubmed:abstractText |
Gene knockout approaches have helped to better understand the functions of the different Y receptors. However, some results obtained from these knockout mice are unexpected and differ from the results of pharmacological intervention experiments. One possible explanation for this is that germ-line gene deletion of a particular Y receptor can influence expression and function of the remaining Y receptors. Here we show that such compensation in mRNA and protein expression does occur in Y receptor single, double and triple knockout models. Radio-ligand binding experiments using [(125)I]-PYY revealed significant up- and down-regulation of remaining Y receptor binding sites in various Y receptor knockout models compared to results from control mice employing Y receptor preferring agonist or antagonists for displacement of the radio-ligand. The most obvious change can be seen in the hippocampus of Y(1) knockout mice, where the level of the remaining Y receptors is strongly down-regulated. In Y(2) knockout mice no such trend can be seen, however, the expression pattern is significantly changed with a strong up-regulation of [(125)I]-PYY specific binding in the dentate gyrus. Interestingly, this pattern was also seen in Y(1)Y(2)Y(4) triple knockout mice. Y(5) receptor mRNA was approximately 20% higher in the hippocampus and dentate gyrus in the triple knockout mice compared to wild-type controls, while Y(6) mRNA expression could not be detected. However, competition binding experiments in Y(1)Y(2)Y(4) triple knockout mice with the Y(5) receptor preferring ligands [Leu(31), Pro(34)] NPY and [A(31), Aib(32)] NPY were able to replace only approximately 50% of [(125)I]-PYY binding in the dentate gyrus suggesting the existence of further yet unidentified Y receptor(s).
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Iodine Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide YY,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neuropeptide Y,
http://linkedlifedata.com/resource/pubmed/chemical/neuropeptide Y-Y1 receptor,
http://linkedlifedata.com/resource/pubmed/chemical/neuropeptide Y2 receptor,
http://linkedlifedata.com/resource/pubmed/chemical/neuropeptide Y4 receptor,
http://linkedlifedata.com/resource/pubmed/chemical/neuropeptide Y5 receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0143-4179
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
39
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
21-8
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15627497-Animals,
pubmed-meshheading:15627497-Brain Stem,
pubmed-meshheading:15627497-Hippocampus,
pubmed-meshheading:15627497-Hypothalamus,
pubmed-meshheading:15627497-Iodine Radioisotopes,
pubmed-meshheading:15627497-Ligands,
pubmed-meshheading:15627497-Mice,
pubmed-meshheading:15627497-Mice, Knockout,
pubmed-meshheading:15627497-Peptide YY,
pubmed-meshheading:15627497-Receptors, Neuropeptide Y
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pubmed:year |
2005
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pubmed:articleTitle |
Compensatory changes in [125I]-PYY binding in Y receptor knockout mice suggest the potential existence of further Y receptor(s).
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pubmed:affiliation |
Neurobiology Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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