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

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Adenosine

Abstract

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.

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Abbreviations

5′NT:

5′-Nucleotidases

A1 receptor/A2A receptor/A2B receptor/A3 receptor:

A1R/A2AR/A2BR/A3R subtype of adenosine receptors

AC:

Adenylate cyclase

ADA:

Adenosine deaminase

Ade:

Adenine

ADK:

Adenosine kinase

Ado:

Adenosine

AMP:

Adenosine monophosphate

CDP-choline:

Cytidine diphosphocholine

cN:

Cytoplasmic 5′-nucleotidases

CNS:

Central nervous system

CNT transporters:

Concentrative nucleoside transporters

CNT1/CNT2/CNT3 transporters:

CNT1/CNT2/CNT3 subtype of concentrative nucleoside transporters

Cyd:

Cytidine

EC:

Extracellular

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

GABA:

γ-Aminobutyric acid

GDA:

Guanine deaminase

GMP:

Guanosine monophosphate

Gn:

Guanine

Guo:

Guanosine

Hyp:

Hypoxanthine

IMP:

Inosine monophosphate

Ino:

Inosine

NBTI:

S-(4-nitrobenzyl)-6-thioinosine

PLC:

Phospholipase C

PNP:

Purine nucleoside phosphorylase

Urd:

Uridine

Xn:

Xanthine

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Acknowledgments

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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Authors and Affiliations

  1. Department of Zoology, University of West Hungary, Savaria Campus, Károlyi Gáspár tér 4, Szombathely, 9700, Hungary

    Zsolt Kovács

  2. Neuromorphological and Neuroendocrine Research Laboratory, Department of Anatomy, Histology and Embryology, Semmelweis University and the Hungarian Academy of Sciences, Budapest, Hungary

    Arpád Dobolyi

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  1. Zsolt Kovács
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  2. Arpád Dobolyi
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Correspondence to Zsolt Kovács .

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  1. Trinity College, 300 Summit Street, LSC 208, Hartford, 06106, USA

    Susan Masino

  2. Legacy Research Institute, Portland, OR,, 1225 NE 2nd Avenue, Portland, 97232, USA

    Detlev Boison

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Kovács, Z., Dobolyi, A. (2013). Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy. In: Masino, S., Boison, D. (eds) Adenosine. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3903-5_29

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