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| Home > Publications database > Adenosine A(1) receptors in human brain and transfected CHO cells: inhibition of [(3)H]CPFPX binding by adenosine and caffeine |
| Home > Publications database > Adenosine A(1) receptors in human brain and transfected CHO cells: inhibition of [(3)H]CPFPX binding by adenosine and caffeine |
| Journal Article | PreJuSER-12002 |
; ; ;
2011
Elsevier Science
Amsterdam [u.a.]
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Please use a persistent id in citations: doi:10.1016/j.neulet.2010.10.068
Abstract: In vivo imaging of adenosine function has become feasible with the specific A(1) adenosine receptor ligand [(18)F]CPFPX and positron emission tomography (PET). It is, however, still an open question whether [(18)F]CPFPX is displaceable by endogenous adenosine, which would allow to detect activity-dependent adenosine release in vivo. We used the tritiated analog of [(18)F]CPFPX, [(3)H]CPFPX, to quantify A(1) adenosine receptors (A(1)AR) in grey matter tissue homogenates of four human brains and A(1)AR transfected Chinese hamster ovary cells, respectively. Saturation binding experiments in the presence of a stable GTP analog revealed a dissociation constant (K(D)) of 2.4±0.5nM. The unselective endogenous A(1)AR agonist adenosine and the antagonist caffeine displaced specific [(3)H]CPFPX binding completely at high doses. Concentrations sufficient to inhibit 50% of binding (IC(50)) were 6.9±2.7μM for adenosine and 148±15.4μM for caffeine. Respective inhibition constants (K(i)) were 2.8±0.9μM and 61.4±11.2μM.The present report supports the possibility of studying acute effects of adenosine and caffeine in vivo with [(18)F]CPFPX and PET. Pathophysiological conditions like hypoxia which increase endogenous adenosine concentrations several folds might interfere with in vivo [(18)F]CPFPX binding. Caffeine intake previous to the investigation should be considered as a confounding factor regarding the determination of receptor densities with [(18)F]CPFPX and PET.
Keyword(s): Adenosine: pharmacokinetics (MeSH) ; Animals (MeSH) ; Binding, Competitive (MeSH) ; Brain: radionuclide imaging (MeSH) ; CHO Cells (MeSH) ; Caffeine: pharmacokinetics (MeSH) ; Cricetinae (MeSH) ; Cricetulus (MeSH) ; Humans (MeSH) ; Positron-Emission Tomography: methods (MeSH) ; Radiopharmaceuticals: pharmacokinetics (MeSH) ; Receptor, Adenosine A1: metabolism (MeSH) ; Transfection (MeSH) ; Tritium: diagnostic use (MeSH) ; Xanthines: pharmacokinetics (MeSH) ; 8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine ; Radiopharmaceuticals ; Receptor, Adenosine A1 ; Xanthines ; Tritium ; Caffeine ; Adenosine ; J ; Competition (auto) ; Saturation binding (auto) ; CPFPX (auto) ; Adenosine (auto) ; Caffeine (auto) ; Human (auto) ; Brain (auto)
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