%0 Journal Article
%A Elmenhorst, D.
%A Garibotto, V.
%A Prescher, A.
%A Bauer, A.
%T Adenosine A(1) receptors in human brain and transfected CHO cells: inhibition of [(3)H]CPFPX binding by adenosine and caffeine
%J Neuroscience letters
%V 487
%@ 0304-3940
%C Amsterdam [u.a.]
%I Elsevier Science
%M PreJuSER-12002
%P 415 - 420
%D 2011
%Z This work was supported by the Heinrich Hertz Foundation of the Ministry of Science and Technology, North-Rhine Westfalia, Germany to DE and the German Federal Ministry of Education and Research (Brain Imaging Center West, to DE and AB).
%X 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.
%K Adenosine: pharmacokinetics
%K Animals
%K Binding, Competitive
%K Brain: radionuclide imaging
%K CHO Cells
%K Caffeine: pharmacokinetics
%K Cricetinae
%K Cricetulus
%K Humans
%K Positron-Emission Tomography: methods
%K Radiopharmaceuticals: pharmacokinetics
%K Receptor, Adenosine A1: metabolism
%K Transfection
%K Tritium: diagnostic use
%K Xanthines: pharmacokinetics
%K 8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine (NLM Chemicals)
%K Radiopharmaceuticals (NLM Chemicals)
%K Receptor, Adenosine A1 (NLM Chemicals)
%K Xanthines (NLM Chemicals)
%K Tritium (NLM Chemicals)
%K Caffeine (NLM Chemicals)
%K Adenosine (NLM Chemicals)
%K J (WoSType)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:21056087
%U <Go to ISI:>//WOS:000286697400035
%R 10.1016/j.neulet.2010.10.068
%U https://juser.fz-juelich.de/record/12002