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• Vol.47 No.11
• CLINICA NEUROL, 47: 835−837, 2007
• Vol.47 No.11 contents

The 48th Annual Meeting of the Japanese Society of Neurology

Adenosine receptor -relation to dopaminergic system-

Masahiro Mishina, M.D.¹⁾²⁾, Kenji Ishii, M.D.²⁾ and Kiichi Ishiwata, Ph.D.²⁾

¹⁾Neurological Institute, Nippon Medical School Chiba Hokusoh Hospital
²⁾Positron Medical Center, Tokyo Metropolitan Institute of Gerontology

Adenosine is produced by conversion of intra- and extracellular adenine nucleotides, and plays a role as an endogenous modulator of synaptic functions in the central nervous system. The adenosine A_2A receptors (A_2AR) are enriched in dopamine-rich areas of the brain, such as the basal ganglia, and are thought to interact with dopamine D₂ receptor (D₂R) negatively. Selective A_2AR antagonists have attracted attention as the treatment of Parkinson's disease (PD). Little information was available about the receptor in the living human brain until quite recently. However, we developed a PET ligand, [7-methyl-¹¹C]-(E)-8- (3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([¹¹C]TMSX), for mapping the A_2AR. We reported that the binding potential (BP) of[¹¹C]TMSX in normal human brain was the largest in the putamen, and was small in the cerebral cortex. Next, we investigated the relationship between A_2AR in the drug naive PD. We found that the BP of[¹¹C]TMSX was significantly lower on the more affected side than the less affected side of the putamen in PD patients. Release of dopamine is reduced asymmetrically in the putamen of early PD, and D₂R are up-regulated as compensation for the decrease of dopamine. Our data showed that reaction of the A_2AR was opposite to the D₂R.

(CLINICA NEUROL, 47: 835−837, 2007)
key words: adenosine A_2A receptor, positron emission tomography, adenosine A₁ receptor, dopamine, Parkinson's disease

(Received: 16-May-07)