Source:http://linkedlifedata.com/resource/pubmed/id/17845212
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2007-9-11
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| pubmed:abstractText |
The density of beta2-adrenoceptors is significantly decreased in both keratinocytes and peripheral blood lymphocytes from patients with atopic eczema. Furthermore both cell types showed a sixfold increase in the K(D) for the specific binding of the non-specific antagonists (-)-[(3)H]CGP 12177 and [(125) I]CYP to keratinocytes and lymphocytes respectively compared with healthy controls. Based on these results polymorphism in the beta2-adrenoceptor gene was suspected. Consequently the entire intronless beta2-adrenoceptor gene was isolated from whole blood and by RT-PCR from keratinocyte extracts of nine patients with atopic eczema and four healthy controls. DNA sequence analysis of nine atopic eczema patients confirmed a substitution in codon (1618) GCC (Ala(119)) to GAC (Asp(119)). This point mutation is expressed on the third transmembrane helix only 13A away from the established agonist/antagonist binding site at Asp(113). Computer modelling of this third transmembrane helix revealed substantial structural changes in the mutant compared with the wild type. Epidermal keratinocytes were established from one patient with atopic eczema (homozygote), the mother (heterozygote) and one age-matched healthy control. Cells were grown in media containing different concentrations of l-phenylalanine and receptor densities were determined. The results showed that cells with atopic eczema showed an increased sensitivity to l-phenylalanine concentrations with a narrow homeostasis compared with healthy controls. The heterozygous mother was only 50% as sensitive as the child. In summary, the results indicate that atopic eczema is associated with a single point mutation in the beta2-adrenoceptor gene leading to an impaired adrenergic response in the epidermis of these patients.
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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/Adrenergic beta-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/CGP 12177,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylalanine,
http://linkedlifedata.com/resource/pubmed/chemical/Propanolamines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta-2
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0906-6705
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
16
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
807-13
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| pubmed:meshHeading |
pubmed-meshheading:17845212-Adolescent,
pubmed-meshheading:17845212-Adrenergic beta-Antagonists,
pubmed-meshheading:17845212-Adult,
pubmed-meshheading:17845212-Amino Acid Sequence,
pubmed-meshheading:17845212-Amino Acid Substitution,
pubmed-meshheading:17845212-Base Sequence,
pubmed-meshheading:17845212-Binding, Competitive,
pubmed-meshheading:17845212-Child,
pubmed-meshheading:17845212-DNA Mutational Analysis,
pubmed-meshheading:17845212-Dermatitis, Atopic,
pubmed-meshheading:17845212-Female,
pubmed-meshheading:17845212-Humans,
pubmed-meshheading:17845212-Keratinocytes,
pubmed-meshheading:17845212-Leukocytes, Mononuclear,
pubmed-meshheading:17845212-Male,
pubmed-meshheading:17845212-Models, Molecular,
pubmed-meshheading:17845212-Molecular Sequence Data,
pubmed-meshheading:17845212-Phenylalanine,
pubmed-meshheading:17845212-Point Mutation,
pubmed-meshheading:17845212-Propanolamines,
pubmed-meshheading:17845212-Protein Structure, Secondary,
pubmed-meshheading:17845212-Radioligand Assay,
pubmed-meshheading:17845212-Receptors, Adrenergic, beta-2
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| pubmed:year |
2007
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| pubmed:articleTitle |
Structural and functional alterations in the beta2-adrenoceptor are caused by a point mutation in patients with atopic eczema.
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| pubmed:affiliation |
Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, Bradford, UK. k.schallreuter@bradford.ac.uk
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| pubmed:publicationType |
Journal Article
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