Depression of NMDA-Evoked Acetylcholine Release by Endogenous Adenosine in Striatum Slices
The mechanisms of NMDA-evoked transmitter release are still not clear. We demonstrate for the first time that NMDA-evoked acetylcholine release is depressed by endogenous liberated adenosine in functionally-hypoxic and non-hypoxic brain slices. Adenosine deaminase potentiates the release of 3H-acetylcholine from rat striatum slices in response to N-Methyl-D-Aspartate (NMDA) stimulation, whereas (-)-R-phenylisopropyl-adenosine (R-PIA) decreases the NMDA-evoked transmitter release. The NMDA-evoked transmitter release is potentiated by 8-cyclopentyl-l,3-dipropylxanthine (DPCPX) only in adenosine depleted slices. The increase of extraneuronal adenosine by dipyridamole also depresses the presynaptic transmitter release.
Our results indicate: (i) that stimulation of NMDA-receptors induces a complex neuronal response, e.g., release of acetylcholine and release of adenosine, (ii) that adenosine induces an agonist high affinity conformation of the A1-receptors which apparently are insensitive to an A1 -adenosine receptor-antagonist (DPCPX) and (iii) that brain slices 0.5 mm thick can serve as an experimental model for testing antihypoxic substances.
KeywordsAdenosine Receptor Adenosine Deaminase Transmitter Release Thick Slice Ibotenic Acid
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