Source:http://linkedlifedata.com/resource/pubmed/id/12450563
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| rdf:type | |
| lifeskim:mentions | |
| pubmed:dateCreated |
2002-11-26
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| pubmed:abstractText |
Study of the CC chemokine receptor 3 (CCR3) has been limited to using radiolabeled agonist chemokines. A small molecule CCR3 antagonist, 2-[(6-amino-2-benzothiazolyl)thio]-N-[1-[(3,4-dichlorylphenyl)methyl]-4-piperidinyl]acetamide, Banyu (I), was tritiated and used for pharmacological studies. Banyu (I) has a K(d) of 5.0+/-0.4 and 4.3+/-1.8 nM on human CCR3 transfectants and eosinophils, and noncompetitively inhibits [125I]eotaxin binding and eotaxin-induced [35S]guanosine-5'-O-(3-thiotriphosphate) ([35S]GTPgammaS) binding. The proportion of [125I]eotaxin: [3H]Banyu (I) binding sites in eosinophils or transfectants was 35% or 13%, although both binding sites were overexpressed in transfectants. CCR3 spontaneously couples to G-proteins in CCR3 transfectants, demonstrated by changes in basal and eotaxin-induced [35S]GTPgammaS binding under reduced NaCl and GDP concentrations. Consequently, Banyu (I) was identified as an inverse agonist. In contrast, CCL18 and I-TAC (interferon-inducible T cell alpha-chemoattractant) were neutral antagonists, inhibiting eotaxin-induced [35S]GTPgammaS binding, with minimal effect on basal coupling of CCR3 to G proteins. Eotaxin, eotaxin-2 and monocyte chemoattractant protein (MCP)-4 are full agonists inducing [35S]GTPgammaS binding; eotaxin-3, MCP-3, RANTES (regulated on activation normal T cell expressed and secreted), vMIP-I (Kaposi's sarcoma-associated herpesvirus macrophage inflammatory protein-) and vMIP-II are partial agonists, indicating that this is a sensitive method to quantitate agonist efficacy.
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| pubmed:language |
eng
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| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCL11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CCL13 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CCR3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ccl11 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Ccr3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL11,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL5,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CC,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine 5'-O-(3-Thiotriphosphate),
http://linkedlifedata.com/resource/pubmed/chemical/Monocyte Chemoattractant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR3,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Chemokine,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfur Radioisotopes
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| pubmed:status |
MEDLINE
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| pubmed:author |
pubmed-author:BillahM MotasimMM,
pubmed-author:EganR WRW,
pubmed-author:GarlisiCharles GCG,
pubmed-author:HeskDavidD,
pubmed-author:JakwayJames PJP,
pubmed-author:QiuHongchenH,
pubmed-author:ShahHimanshuH,
pubmed-author:TianFangF,
pubmed-author:TingPaulineP,
pubmed-author:UmlandShelby PSP,
pubmed-author:WanYuntaoY
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1-10
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| pubmed:dateRevised |
2007-11-15
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| pubmed:articleTitle |
Identification of full, partial and inverse CC chemokine receptor 3 agonists using [35S]GTPgammaS binding.
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| pubmed:affiliation |
Department of Allergy, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
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