• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.175-182
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• 1993

As it has been reported that the depolarization-induced ACh release is modulated by activation of presynaptic $A_1-adenosine$ heteroreceptor in hippocampus and various lines of evidence indicate the adenosine effect is magnesium dependent, the present study was undertaken to delineate the role of endogenus adenosine as a modulator of hippocampal acetylcholine release in this study. Slices from the rat hippocampus were equilibrated with $[^3H]-choline$ and the release of the labelled product, $[^3H]-ACh$, was evoked by electrical stimulation(3Hz, $5\;V\;cm^{-1},$ 2ms, rectangular pulses), and the influence of various agents on the evoked tritium outflow was investigated. Adenosine, in concentrations ranging from $0.3\;to\;100\;{\mu}M$, decreased the $[^3H]-ACh$ release in a dose-dependent manner without changing the basal rate of release. $DPCPX(1{\sim}10{\mu}M)$, a selective $A_1-receptor$ antagonist, increased the $[^3H]-ACh$ release in a dose-related fashion with slight increase of basal tritium release. And the effects of adenosine were significantly inhibited by $DPCPX(2{\mu}M)$ treatment. CPCA, a specific $A_2-agonist$, in concentration ranging from $0.3\;to\;30\;{\mu}M$ decreased evoked tritium outflow with increase of basal rate of tritium release, and these effects were also abolished by $DPCPX(2{\mu}M)$ pretreatment. But, $CGS(0.1{\sim}10{\mu}M)$, a recently introduced potent $A_2-agonist$, did not alter the evoked tritium outflow. When the magnesium concentration of the medium was reduced to 0 mM, there was no change in evoked ACh release by adenosine. In contrast, increasing the magnesium concentration to 4 mM, the inhibitory effects of adenosine were significantly potentiated. These results indicate that $A_1-adenosine$ heteroreceptor is involved in ACh-release in the rat hippocampus and the inhibitory effects of adenosine mediated by $A_1-receptor$ is magnesium-dependent.