Uridine release during aminopyridine-induced epilepsy

Slézia, Andrea; Kékesi, Katalin A.; Szikra, Tamás; Papp, Andrea; Nagy, K.; Szente, Magdolna; Maglóczky, Zs.; Freund, Tamás F.; Juhász, Gábor

doi:10.1016/j.nbd.2004.02.011

Cited by 43 publications

(35 citation statements)

References 64 publications

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“…Their concentrations in the rat striatum, hippocampus and thalamus were 1.50-2.00, 0.42-1.37 and 0.52 M, respectively, for Ino and 0.50, 0.26 and 0.17 M, respectively, for Guo. Concentrations of Urd were similar in the rat thalamus (0.76 M) and hippocampus (0.71 M) [112,[123][124][125][126]. Activity of PNP was intermediate to high in the cerebral cortex and thalamus [348], whereas intermediate levels of GDA activity were demonstrated in the hippocampus and parietal cortex of the human brain.…”

Section: Non-adenosine Nucleosides: Uridine Guanosine and Inosinementioning

confidence: 78%

“…In addition, the highest Ado immunoreactivity was determined in the pyramidal cells of the hippocampus and granule cells of the dentate gyrus [122]. Approximately two-fold higher EC Ado levels were measured in the rat striatum (1.92 M) than in the hippocampus (0.93-0.95 M) and thalamus (0.95 M) [112,[123][124][125][126]. In addition, uneven distributions of ADA activity and ADK activity, which may regulate Ado levels in the brain tissue, were revealed in the different brain areas.…”

Section: Modulation Of Adenosine Levels and Epileptic Activity By Metmentioning

confidence: 96%

“…The inhibition by Ado may be sufficient (i) to regulate the spreading of seizures, (ii) to decrease epileptic activity ( Table 3) and (iii) for seizure termination [96,101,[103][104][105][106][107][108]. An increase in the Ado level in epileptic brain tissue has been demonstrated [109][110][111][112]. Consequently, increasing the Ado level in the brain by specific inhibitors of nucleoside metabolic enzymes (e.g., ADA and ADK inhibitors) and nucleoside transporters ( Table 2; Fig.…”

Section: Adenosinementioning

confidence: 99%

“…Indeed, the anticonvulsant effect of Urd has been demonstrated. Uridine reduced penicillin-, bicuculline-and PTZinduced seizures and was effective in electroconvulsive models ( Table 4) but did not protect against maximal electroshock-induced convulsions and 3-aminopyridine-induced seizures [112,[350][351][352][353][354]. However, it has been postulated that Urd may have a role in the initiation and termination of epileptic activity depending on its concentration [352].…”

Section: Non-adenosine Nucleosides: Uridine Guanosine and Inosinementioning

confidence: 99%

“…More recently, Urd was found to be antiepileptogenic in hippocampal kindling models and in lithium-pilocarpine-induced status epilepticus in rats [63,64]. In addition, an increased Urd level was detected in 3-aminopyridine-(3-AP)-induced epileptic seizures, which most likely inhibits neuronal activity [112], and Urd reduces the firing rate of neurons in the hippocampus [59]. It has also been demonstrated by Dobolyi et al [59] that Urd administration had no effect on the EC Ado concentration; thus, direct involvement of the adenosinergic system in an Urd-induced decrease in epileptic activity is not likely.…”

Section: Non-adenosine Nucleosides: Uridine Guanosine and Inosinementioning

confidence: 99%

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The Antiepileptic Potential of Nucleosides

Kovács¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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Despite newly developed antiepileptic drugs to suppress epileptic symptoms, approximately one third of patients remain drug refractory. Consequently, there is an urgent need to develop more effective therapeutic approaches to treat epilepsy. A great deal of evidence suggests that endogenous nucleosides, such as adenosine (Ado), guanosine (Guo), inosine (Ino) and uridine (Urd), participate in the regulation of pathomechanisms of epilepsy. Adenosine and its analogues, together with non-adenosine (non-Ado) nucleosides (e.g., Guo, Ino and Urd), have shown antiseizure activity. Adenosine kinase (ADK) inhibitors, Ado uptake inhibitors and Ado-releasing implants also have beneficial effects on epileptic seizures. These results suggest that nucleosides and their analogues, in addition to other modulators of the nucleoside system, could provide a new opportunity for the treatment of different types of epilepsies. Therefore, the aim of this review article is to summarize our present knowledge about the nucleoside system as a promising target in the treatment of epilepsy.

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Section: Non-adenosine Nucleosides: Uridine Guanosine and Inosinementioning

confidence: 78%

Section: Modulation Of Adenosine Levels and Epileptic Activity By Metmentioning

confidence: 96%

Section: Adenosinementioning

confidence: 99%

Section: Non-adenosine Nucleosides: Uridine Guanosine and Inosinementioning

confidence: 99%

Section: Non-adenosine Nucleosides: Uridine Guanosine and Inosinementioning

confidence: 99%

See 3 more Smart Citations

The Antiepileptic Potential of Nucleosides

Kovács¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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Microdialysis as a Tool to Unravel Neurobiological Mechanisms of Seizures and Antiepileptic Drug Action

Smolders

Clinckers

Michotte

2011

Applications of Microdialysis in Pharmaceutical Science

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Pathological Potential of Astroglial Purinergic Receptors

Franke

Illéš

2014

Advances in Neurobiology

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Acute brain injury and neurodegenerative disorders may result in astroglial activation. Astrocytes are able to determine the progression and outcome of these neuropathologies in a beneficial or detrimental way. Nucleotides, e.g. adenosine 5'-triphosphate (ATP), released after acute or chronic neuronal injury, are important mediators of glial activation and astrogliosis.Acute injury may cause significant changes in ATP balance, resulting in (1) a decline of intracellular ATP levels and (2) an increase in extracellular ATP concentrations via efflux from the intracellular space. The released ATP may have trophic effects, but can also act as a proinflammatory mediator or cytotoxic factor, inducing necrosis/apoptosis as a universal "danger" signal. Furthermore, ATP, primarily released from astrocytes, is a means of communication between neurons, glial cells, and intracerebral blood vessels.Astrocytes express a heterogeneous battery of purinergic ionotropic and metabotropic receptors (P2XRs and P2YRs, respectively) to respond to extracellular nucleotides.In this chapter, we summarize the contemporary knowledge on the pathological potential of P2Rs in relation to changes of astrocytic functions, determined by distinct molecular signaling cascades, in a variety of diseases. We discuss specific aspects of reactive astrogliosis, with respect to the involvement of prominent receptor subtypes, such as the P2X7 and P2Y1/2Rs. Examples of purinergic signaling of microglia, oligodendrocytes, and blood vessels under pathophysiological conditions will also be presented.The understanding of the pathological potential of purinergic signaling in "controlling and fine-tuning" of astrocytic responses is important for identifying possible therapeutic principles to treat acute and chronic central nervous system diseases.

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Uridine release during aminopyridine-induced epilepsy

Cited by 43 publications

References 64 publications

The Antiepileptic Potential of Nucleosides

The Antiepileptic Potential of Nucleosides

Microdialysis as a Tool to Unravel Neurobiological Mechanisms of Seizures and Antiepileptic Drug Action

Pathological Potential of Astroglial Purinergic Receptors

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