TY  - JOUR
AU  - Elmenhorst, D.
AU  - Garibotto, V.
AU  - Prescher, A.
AU  - Bauer, A.
TI  - Adenosine A(1) receptors in human brain and transfected CHO cells: inhibition of [(3)H]CPFPX binding by adenosine and caffeine
JO  - Neuroscience letters
VL  - 487
SN  - 0304-3940
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - PreJuSER-12002
SP  - 415 - 420
PY  - 2011
N1  - 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).
AB  - 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.
KW  - Adenosine: pharmacokinetics
KW  - Animals
KW  - Binding, Competitive
KW  - Brain: radionuclide imaging
KW  - CHO Cells
KW  - Caffeine: pharmacokinetics
KW  - Cricetinae
KW  - Cricetulus
KW  - Humans
KW  - Positron-Emission Tomography: methods
KW  - Radiopharmaceuticals: pharmacokinetics
KW  - Receptor, Adenosine A1: metabolism
KW  - Transfection
KW  - Tritium: diagnostic use
KW  - Xanthines: pharmacokinetics
KW  - 8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine (NLM Chemicals)
KW  - Radiopharmaceuticals (NLM Chemicals)
KW  - Receptor, Adenosine A1 (NLM Chemicals)
KW  - Xanthines (NLM Chemicals)
KW  - Tritium (NLM Chemicals)
KW  - Caffeine (NLM Chemicals)
KW  - Adenosine (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:21056087
UR  - <Go to ISI:>//WOS:000286697400035
DO  - DOI:10.1016/j.neulet.2010.10.068
UR  - https://juser.fz-juelich.de/record/12002
ER  -