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Characterization of Basal and Morphine-Induced Uridine Release in the Striatum: An In Vivo Microdialysis Study in Mice

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Abstract

Uridine, a pyrimidine nucleoside, has been proposed to be a potential signaling molecule in the central nervous system. The understanding of uridine release in the brain is therefore of fundamental importance. The present study was performed to determine the characteristics of basal and morphine-induced uridine release in the striatum of freely moving mice by using the microdialysis technique. To ascertain whether extracellular uridine was derived from neuronal release, the following criteria were applied: sensitivity to (a) K+ depolarization, (b) Na+ channel blockade and (c) removal of extracellular Ca2+. Uridine levels were not greatly affected by infusion of tetrodotoxin (TTX) and were unaffected by either Ca2+-free medium or in the presence of EGTA (a calcium chelator), suggesting that basal extracellular uridine levels were maintained mainly by non-vesicular release mechanisms. In addition, both systemic and local application of morphine increased striatal uridine release. The morphine-induced release was reversed by naloxone pretreatment, but was unaffected by TTX or EGTA infusion. Moreover, co-administration of morphine and nitrobenzylthioinosine (NBTI, an inhibitor of nucleotide transporter) produced increases of uridine levels similar to that produced by NBTI or morphine alone, suggesting a nucleotide transporter mechanism involved. Taken together, these findings suggest that morphine produces a μ-opioid receptor-mediated uridine release via nucleoside transporters in a TTX- and calcium-independent manner.

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Acknowledgments

This research is partly supported by the Project of Key Laboratory for New Drug Screening, Key Laboratory for Pharmacodynamics, of Liaoning Province, and by the National Key Scientific Project for New Drug Discovery and Development, (2010ZX09401-304), 2010-2012, P. R. China.

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Authors and Affiliations

  1. Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, Shenyang, 110016, People’s Republic of China

    Wu Song, Chun-Fu Wu, Ping Liu, Fang Wang, Ying-Xu Dong & Jing-Yu Yang

  2. Mathematics Teaching & Research Section, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China

    Rong-Wu Xiang

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  1. Wu Song
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  2. Chun-Fu Wu
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Correspondence to Jing-Yu Yang.

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Song, W., Wu, CF., Liu, P. et al. Characterization of Basal and Morphine-Induced Uridine Release in the Striatum: An In Vivo Microdialysis Study in Mice. Neurochem Res 38, 153–161 (2013). https://doi.org/10.1007/s11064-012-0903-1

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  • DOI: https://doi.org/10.1007/s11064-012-0903-1

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