Uridine function in the central nervous system.

Neuromorphological and Neuroendocrine Research Laboratory, Department of Anatomy, Histology and Embryology,Semmelweis University and the Hungarian Academy of Sciences, H-1094 Budapest, Hungary.
Current topics in medicinal chemistry (Impact Factor: 4.47). 03/2011; 11(8):1058-67. DOI: 10.2174/156802611795347618
Source: PubMed

ABSTRACT In the adult nervous system, the major source of nucleotide synthesis is the salvage pathway. Uridine is the major form of pyrimidine nucleosides taken up by the brain. Uridine is phosphorylated to nucleotides, which are used for DNA and RNA synthesis as well as for the synthesis of membrane constituents and glycosylation. Uridine nucleotides and UDP-sugars may be released from neuronal and glial cells. Plasmamembrane receptors of 7 transmembrane domains have been identified that recognize UTP, UDP, and UDP-sugar conjugates. These receptors are called P2Y2 and P2Y4, P2Y6, and P2Y14 receptors, respectively. In addition, binding sites for uridine itself have also been suggested. Furthermore, uridine administration had sleep-promoting and anti-epileptic actions, improved memory function and affected neuronal plasticity. Information only starts to be accumulating on potential mechanisms of these uridine actions. Some data are available on the topographical distribution of pyrimidine receptors and binding sites in the brain, however, their exact role in neuronal functions is not established yet. There is also a scarcity of data regarding the brain distribution of other components of the pyrimidine metabolism although site specific functions exerted by their receptors might require different metabolic support. Despite the gaps in our knowledge on the neuronal functions of pyrimidine nucleosides, their therapeutic utilization is appealing. They have been suggested for the treatment of epileptic and neurodegenerative diseases as neuroprotective agents. In addition, the development of traditional drugs acting specifically on pyrimidine receptor subtypes is also promising as a new direction to treat neurological disorders.

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    ABSTRACT: Adenosine (Ado) and some non-adenosine (non-Ado) nucleosides including inosine (Ino), guanosine (Guo) and uridine (Urd) are modulatory molecules in the central nervous system (CNS), regulating different physiological and pathophysiological processes in the brain such as sleep and epilepsy. Indeed, different drugs effective on adenosinergic system (e.g., Ado metabolism inhibitors, agonists and antagonists of Ado receptors) are being used in drug development for the treatment of epileptic disorders. Although (i) endogenous Ino, Guo and Urd showed anticonvulsant/antiepileptic effects (e.g., in quinolinic acid - induced seizures and in different epilepsy models such as hippocampal kindling models), and (ii) there is need to generate new and more effective antiepileptic drugs for the treatment of drug-resistant epilepsies, our knowledge about antiepileptic influence of non-Ado nucleosides is far from complete. Thus, in this review article, we give a short summary of anticonvulsant/antiepileptic effects and mechanisms evoked by Ino, Guo, and Urd. Finally, we discuss some non-Ado nucleoside derivatives and their structures, which may be candidates as potential antiepileptic agents.
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