Adenosine pp 621-656 | Cite as

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

  • Zsolt KovácsEmail author
  • Arpád Dobolyi


Nucleosides have a wide range of physiological and pathophysiological roles in the human brain as modulators of a variety of neural functions. For example, adenosine, inosine, guanosine, and uridine participate in the mechanisms underlying memory, cognition, sleep, pain, depression, schizophrenia, epilepsy, Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. Consequently, increasing attention is now being given to the specific role of nucleosides in physiological and pathological processes in the human brain. Different elements of nucleoside system, including nucleoside concentrations, metabolic enzyme activity, and expression of nucleoside transporters and receptors, may be changed under normal and pathological conditions. The alterations suggest that interlinked elements of the nucleoside system are functioning in a tightly concerted manner.

Nucleoside levels, activity of nucleoside metabolic enzymes, and expression of nucleoside transporters and receptors are unevenly distributed in the brain, suggesting that nucleosides have different roles in functionally distinct human brain areas. The aim of this chapter is to summarize our present knowledge of the anatomical distribution of nucleoside system in the human brain, placing emphasis on potential therapeutic pharmacological strategies.


Nucleosides Anatomical distribution of nucleoside system Human brain diseases and therapy 




A1 receptor/A2A receptor/A2B receptor/A3 receptor

A1R/A2AR/A2BR/A3R subtype of adenosine receptors


Adenylate cyclase


Adenosine deaminase




Adenosine kinase




Adenosine monophosphate


Cytidine diphosphocholine


Cytoplasmic 5′-nucleotidases


Central nervous system

CNT transporters

Concentrative nucleoside transporters

CNT1/CNT2/CNT3 transporters

CNT1/CNT2/CNT3 subtype of concentrative nucleoside transporters





ENT transporters

Equilibrative nucleoside transporters

ENT1/ENT2/ENT3/ENT4 transporters

ENT1/ENT2/ENT3/ENT4 subtype of equilibrative nucleoside transporters

“es” nucleoside transporters

Equilibrative, NBTI sensitive type of ENT transporters


γ-Aminobutyric acid


Guanine deaminase


Guanosine monophosphate








Inosine monophosphate






Phospholipase C


Purine nucleoside phosphorylase







This work was supported by the Scientific Foundation of NYME SEK/NYME SEK TTK (2010–2011) Hungary (Zsolt Kovács) and the OTKA NNF2 85612 Research Grant as well as the Bolyai János Grant of the Hungarian Academy of Sciences (Arpád Dobolyi).

Conflict of interest: All authors declare no conflicts of interest.


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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of ZoologyUniversity of West HungarySzombathelyHungary
  2. 2.Neuromorphological and Neuroendocrine Research Laboratory, Department of Anatomy, Histology and EmbryologySemmelweis University and the Hungarian Academy of SciencesBudapestHungary

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