Adenosine A(2A) receptors measured with [C]TMSX PET in the striata of Parkinson's disease patients.

Abstract

Adenosine A(2A) receptors (A2ARs) are thought to interact negatively with the dopamine D(2) receptor (D2R), so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD). However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET) with [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX) in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test). In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test). In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test) but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an important role in regulation of parkinsonism in PD.

• Authors: Masahiro Mishina, Kiichi Ishiwata, Mika Naganawa, Yuichi Kimura, Shin Kitamura, Masahiko Suzuki, Masaya Hashimoto, Kenji Ishibashi, Keiichi Oda, Muneyuki Sakata, Makoto Hamamoto, Shiro Kobayashi, Yasuo Katayama, Kenji Ishii
• Journal: PloS one (PLoS One) Vol. 6 Issue 2 Pg. e17338 (Feb 28 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 21386999 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiparkinson Agents
• KF18446
• Receptor, Adenosine A2A
• Xanthines

Topics

• Aged
• Antiparkinson Agents (therapeutic use)
• Corpus Striatum (diagnostic imaging, metabolism)
• Dyskinesias (complications, diagnostic imaging, drug therapy)
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Models, Biological
• Parkinson Disease (complications, diagnostic imaging, drug therapy, metabolism)
• Positron-Emission Tomography (methods)
• Prognosis
• Receptor, Adenosine A2A (analysis, metabolism, physiology)
• Xanthines