Cerebral A1 adenosine receptors (A1AR) in liver cirrhosis.
OBJECTIVE
The cerebral mechanisms underlying hepatic encephalopathy (HE) are poorly understood. Adenosine, a neuromodulator that pre- and postsynaptically modulates neuronal excitability and release of classical neurotransmitters via A(1) adenosine receptors (A(1)AR), is likely to be involved. The present study investigates changes of cerebral A(1)AR binding in cirrhotic patients by means of positron emission tomography (PET) and [(18)F]CPFPX, a novel selective A(1)AR antagonist.


METHODS
PET was performed in cirrhotic patients (n = 10) and healthy volunteers (n = 10). Quantification of in vivo receptor density was done by Logan's non-invasive graphical analysis (pons as reference region). The outcome parameter was the apparent binding potential (aBP, proportional to B (max)/K (D)).


RESULTS
Cortical and subcortical regions showed lower A(1)AR binding in cirrhotic patients than in controls. The aBP changes reached statistical significance vs healthy controls (p < 0.05, U test with Bonferroni-Holm adjustment for multiple comparisons) in cingulate cortex (-50.0%), precentral gyrus (-40.9%), postcentral gyrus (-38.6%), insular cortex (-38.6%), thalamus (-32.9%), parietal cortex (-31.7%), frontal cortex (-28.6), lateral temporal cortex (-28.2%), orbitofrontal cortex (-27.9%), occipital cortex (-24.6), putamen (-22.7%) and mesial temporal lobe (-22.4%).


CONCLUSIONS
Regional cerebral adenosinergic neuromodulation is heterogeneously altered in cirrhotic patients. The decrease of cerebral A(1)AR binding may further aggravate neurotransmitter imbalance at the synaptic cleft in cirrhosis and hepatic encephalopathy. Different pathomechanisms may account for these alterations including decrease of A(1)AR density or affinity, as well as blockade of the A(1)AR by endogenous adenosine or exogenous xanthines.
Boy
Christian
C
Brain Imaging Centre West, Institute of Medicine, Research Centre Jülich, Jülich, Germany.
Meyer
Philipp T
PT
Kircheis
Gerald
G
Holschbach
Marcus H
MH
Herzog
Hans
H
Elmenhorst
David
D
Kaiser
Hans Juergen
HJ
Coenen
Heinz H
HH
Haussinger
Dieter
D
Zilles
Karl
K
Bauer
Andreas
A
D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D014018:Tissue Distribution; D014970:Xanthines / Q000493:pharmacokinetics*
C468796:8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine; D019275:Radiopharmaceuticals; D043682:Receptor, Adenosine A1; D014970:Xanthines