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Effect of idebenone on adenosine outflow and adenine nucleotide level in hippocampal slices under ischemia-like conditions.

Abstract：

:The effect of idebenone on the changes in adenosine and nucleotide metabolism occurring in hippocampal slices after ischemia-like conditions (superfusion with glucose-free Krebs solution gassed with 95% N2-5% CO2) and during reperfusion with normal Krebs solution was investigated by measuring adenosine and inosine outflow, and adenosine and adenine nucleotide levels by HPLC. Five minutes of ischemia-like conditions brought about an 8- and 4-fold increase in adenosine and inosine outflow 10 min after reperfusion and a 75% increase in the tissue level of adenosine, a 40% decrease in ATP, and a 50% increase in AMP at the end of the ischemic period. Ten minutes after reperfusion, ATP and AMP returned to control values. Idebenone (25-100 microM) brought about a concentration-dependent increase in adenosine and inosine outflow evoked by ischemia-like conditions. Idebenone (50 microM) also increased the adenosine content in hippocampal slices after both ischemia (+150%) and reperfusion (+320%). An 82% increase in ADP, 174% in AMP, and 56% in the total sum of nucleotides, 10 min after reperfusion were found in idebenone treated slices. These results suggest that idebenone enhances adenosine formation after ischemia-like conditions from sources other than AMP, and improves phosphorylating activity during reperfusion. Idebenone, by increasing adenosine and total nucleotide levels, may protect brain tissue from ischemic damage.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Latini S,Pedata F,Pepeu G

doi

10.1016/0014-2999(93)90662-2

subject

Has Abstract

pub_date

1993-11-02 00:00:00

pages

65-70

issue

1

eissn

0014-2999

issn

1879-0712

pii

0014-2999(93)90662-2

journal_volume

249

pub_type

杂志文章

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