Source:http://linkedlifedata.com/resource/pubmed/id/14978250
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2004-2-23
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| pubmed:abstractText |
The present study investigates mRNA and protein levels of A3 adenosine receptors in resting (R) and activated (A) human lymphocytes. The receptors were evaluated by the antagonist radioligand [3H]5-N-(4-methoxyphenyl-carbamoyl)amino-8-propyl-2(2furyl)-pyrazolo-[4,3e]-1,2,4-triazolo-[1,5-c]-pyrimidine ([3H]MRE 3008F20), which yielded Bmax values of 125 +/- 15 and 225 +/- 23 fmol/mg of protein and KD values of 1.79 +/- 0.30 and 1.85 +/- 0.25 nM in R and A cells, respectively. The protein seems to be induced with remarkable rapidity starting at 15 min and reaches a plateau at 30 min. Western blot assays revealed that the up-regulation of the A3 subtype after lymphocyte activation was caused by an increase in an enriched CD4+ cell fraction. Real-time reverse transcription-polymerase chain reaction experiments confirmed the rapid increase of A3 mRNA after T cell activation. Competition of radioligand binding by adenosine ligands displayed a rank order of potency typical of the A3 subtype. Thermodynamic data indicated that the binding is enthalpy- and entropy-driven in both R and A cells, suggesting that the activation process does not involve, at a molecular level, receptor alterations leading to modifications in the A3-related binding mechanisms. Functionally, the up-regulation of A3 adenosine receptors in A versus R cells corresponded to a potency increase of the A3 agonist N6-(3-iodo-benzyl)-2-chloro-adenosine-5'-N-methyluronamide in inhibiting cAMP accumulation (IC50=1.5 +/- 0.4 and 2.7 +/- 0.3 nM, respectively); this effect was antagonized by MRE 3008F20 (IC50=5.0 +/- 0.3 nM). In conclusion, our results provide, for the first time, an in-depth investigation of A3 receptors in human lymphocytes and demonstrate that, under activating conditions, they are up-regulated and may contribute to the effects triggered by adenosine.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0026-895X
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| pubmed:author |
pubmed-author:AvitabileAriannaA,
pubmed-author:BoreaPier AndreaPA,
pubmed-author:CattabrigaElenaE,
pubmed-author:FortiniCinziaC,
pubmed-author:GavioliRiccardoR,
pubmed-author:GessiStefaniaS,
pubmed-author:LeungEdwardE,
pubmed-author:Mac LennanStephenS,
pubmed-author:MerighiStefaniaS,
pubmed-author:VaraniKatiaK
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| pubmed:issnType |
Print
|
| pubmed:volume |
65
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
711-9
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| pubmed:dateRevised |
2004-11-17
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| pubmed:meshHeading |
pubmed-meshheading:14978250-Binding, Competitive,
pubmed-meshheading:14978250-Binding Sites,
pubmed-meshheading:14978250-Blotting, Western,
pubmed-meshheading:14978250-Cyclic AMP,
pubmed-meshheading:14978250-Humans,
pubmed-meshheading:14978250-Kinetics,
pubmed-meshheading:14978250-Lymphocyte Activation,
pubmed-meshheading:14978250-Radioligand Assay,
pubmed-meshheading:14978250-Receptor, Adenosine A3,
pubmed-meshheading:14978250-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:14978250-T-Lymphocytes,
pubmed-meshheading:14978250-Thermodynamics,
pubmed-meshheading:14978250-Up-Regulation
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| pubmed:year |
2004
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| pubmed:articleTitle |
Expression of A3 adenosine receptors in human lymphocytes: up-regulation in T cell activation.
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| pubmed:affiliation |
Department of Clinical and Experimental Medicine, Pharmacology Unit, University of Ferrara, Ferrara, Italy.
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| pubmed:publicationType |
Journal Article
|