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@ARTICLE{Elmenhorst:12002,
author = {Elmenhorst, D. and Garibotto, V. and Prescher, A. and
Bauer, A.},
title = {{A}denosine {A}(1) receptors in human brain and transfected
{CHO} cells: inhibition of [(3){H}]{CPFPX} binding by
adenosine and caffeine},
journal = {Neuroscience letters},
volume = {487},
issn = {0304-3940},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {PreJuSER-12002},
pages = {415 - 420},
year = {2011},
note = {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).},
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.},
keywords = {Adenosine: pharmacokinetics / Animals / Binding,
Competitive / Brain: radionuclide imaging / CHO Cells /
Caffeine: pharmacokinetics / Cricetinae / Cricetulus /
Humans / Positron-Emission Tomography: methods /
Radiopharmaceuticals: pharmacokinetics / Receptor, Adenosine
A1: metabolism / Transfection / Tritium: diagnostic use /
Xanthines: pharmacokinetics /
8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine (NLM
Chemicals) / Radiopharmaceuticals (NLM Chemicals) /
Receptor, Adenosine A1 (NLM Chemicals) / Xanthines (NLM
Chemicals) / Tritium (NLM Chemicals) / Caffeine (NLM
Chemicals) / Adenosine (NLM Chemicals) / J (WoSType)},
cin = {INM-2},
ddc = {610},
cid = {I:(DE-Juel1)INM-2-20090406},
pnm = {Funktion und Dysfunktion des Nervensystems (FUEK409) /
89571 - Connectivity and Activity (POF2-89571)},
pid = {G:(DE-Juel1)FUEK409 / G:(DE-HGF)POF2-89571},
shelfmark = {Neurosciences},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:21056087},
UT = {WOS:000286697400035},
doi = {10.1016/j.neulet.2010.10.068},
url = {https://juser.fz-juelich.de/record/12002},
}