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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0002520,
umls-concept:C0009015,
umls-concept:C0020792,
umls-concept:C0025914,
umls-concept:C0026809,
umls-concept:C0205171,
umls-concept:C0205419,
umls-concept:C0231491,
umls-concept:C0449560,
umls-concept:C0597357,
umls-concept:C0679058,
umls-concept:C1167622,
umls-concept:C1273518,
umls-concept:C1334043,
umls-concept:C1417166,
umls-concept:C1547699,
umls-concept:C2003941,
umls-concept:C2700640
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pubmed:issue |
1
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pubmed:dateCreated |
1992-8-21
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pubmed:abstractText |
Molecular cloning and ligand binding studies have shown the alpha 2 class of adrenergic receptor (alpha 2-AR) to be a family of at least three related subtypes in humans. These studies have not, however, identified distinct subtype-specific functions for these receptors in vivo. It should be possible to extend the analysis of alpha 2-AR subtype function to the animal level through the use of experimental mammalian embryology in mice. To begin this process, we have isolated two mouse genomic clones encoding alpha 2-AR subtypes and expressed these genes in COS-7 cells for binding studies. Sequence homology and ligand binding data allow the assignment of one clone (M alpha 2-4H) as the mouse homolog of the human alpha 2-C4 subtype. The other clone (M alpha 2-10H) closely resembles the human alpha 2-C10 subtype in sequence but binds with significantly lower affinity to yohimbine and rauwolscine, members of a distinct class of bulky alpha 2-selective antagonists commonly used to evaluate alpha 2-AR function in vivo. To define the domain(s) responsible for this unusual binding property, we constructed a series of M alpha 2-10H/human alpha 2-C10 chimeric receptors. Analysis of these receptors identified a conservative Cys201 to Ser201 change in the fifth transmembrane domain of M alpha 2-10H as being responsible for the low affinity of the mouse receptor for yohimbine.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acids,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Yohimbine,
http://linkedlifedata.com/resource/pubmed/chemical/atipamezole
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
42
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
16-27
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:1353249-Adrenergic alpha-Antagonists,
pubmed-meshheading:1353249-Amino Acid Sequence,
pubmed-meshheading:1353249-Amino Acids,
pubmed-meshheading:1353249-Animals,
pubmed-meshheading:1353249-Base Sequence,
pubmed-meshheading:1353249-Binding, Competitive,
pubmed-meshheading:1353249-Blotting, Southern,
pubmed-meshheading:1353249-Cloning, Molecular,
pubmed-meshheading:1353249-DNA,
pubmed-meshheading:1353249-Imidazoles,
pubmed-meshheading:1353249-Mice,
pubmed-meshheading:1353249-Mice, Inbred BALB C,
pubmed-meshheading:1353249-Molecular Sequence Data,
pubmed-meshheading:1353249-Receptors, Adrenergic, alpha,
pubmed-meshheading:1353249-Sequence Homology, Nucleic Acid,
pubmed-meshheading:1353249-Species Specificity,
pubmed-meshheading:1353249-Yohimbine
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pubmed:year |
1992
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pubmed:articleTitle |
Cloning of two mouse genes encoding alpha 2-adrenergic receptor subtypes and identification of a single amino acid in the mouse alpha 2-C10 homolog responsible for an interspecies variation in antagonist binding.
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pubmed:affiliation |
Department of Molecular and Cellular Physiology, Stanford University, California 94305.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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