Characterization of basal and morphine-induced uridine release in the striatum: an in vivo microdialysis study in mice.
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 Ca(2+). Uridine levels were not greatly affected by infusion of tetrodotoxin (TTX) and were unaffected by either Ca(2+)-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.
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, Shenyang 110016, People's Republic of China.
Wu
W
Song
Chun-Fu
CF
Wu
Ping
P
Liu
Rong-Wu
RW
Xiang
Fang
F
Wang
Ying-Xu
YX
Dong
Jing-Yu
JY
Yang
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D051379:Mice; D017551:Microdialysis; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D033704:Nucleotide Transport Proteins / Q000096:biosynthesis / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014529:Uridine / Q000378:metabolism*
D002614:Chelating Agents; D009292:Narcotic Antagonists; D009294:Narcotics; D033704:Nucleotide Transport Proteins; D017450:Receptors, Opioid, mu; D026941:Sodium Channel Blockers; D009270:Naloxone; D013779:Tetrodotoxin; D004533:Egtazic Acid; D009020:Morphine; D002118:Calcium; D014529:Uridine