Abstract
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.
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References
Barrington, W. W., Jacobson, K. A., and Stiles, G. L., 1989, Demonstration of distinct agonist and antagonist conformation of A -adenosine receptor, J. Biol. Chem., 264:13157–13164.
Fink, K., Göthert, M., Molderings, G., and Schlicker, E., 1989, N-methyl-D-aspartate (NMDA) receptor-mediated stimulation of noradrenaline release, but not release of other neurotransmitters, in the rat brain cortex: receptor location, characterization and desensitization, Naunyn-Schmiedeberg’s Arch. Pharmacol., 339:514–521.
Fredholm, B. B., Fastbom, J., Duner-Engstrom, M., Hu P.-Sch., van der Ploeg, I., and Dunwiddie, T. V., 1989, Mechanism(s) of inhibition of transmitter release by adenosine receptor activation, in: “Adenosine receptors in the nervous system,” J. A. Ribeiro, ed., Taylor & Francis, London, New York, Philadelphia, 123–131.
Haas, H. L., and Greene, R. W., 1988, Endogenous adenosine inhibits hippocampal CA neurones: further evidence from extra-and intracellular recording, Naunyn-Schmiedeberg’s Arch. Pharmacol., 337:561–565.
Hoehn, K., and White, T., 1990, Role for excitatory amino acid receptors in K+ -and glutamate-evoked release of endogenous adenosine from rat cortical slices, J. Neurochem., 54:256–265.
Jackisch, R., Strittmatter, H., Kasakow, L., and Hertting, G., 1984, Endogenous adenosine as a modulator of hippocampal acetylcholine release, Naunyn-Schmiedeberg’s Arch. Pharmacol., 327:319–325.
Limberger, N., Späth, L., and Starke, K., 1988, Presynaptic a -adrenoceptor, opioid K-receptor and adenosine A -receptor interactions on noradrenaline release in rabbit brain cortex, Naunyn-Schmiedeberg ’s Arch. Pharmacol., 338:53–61.
Porsche-Wiebking, E., 1989, New N-Methyl-D-Aspartate antagonists for the treatment of stroke, Drug Develop. Res., 17:367–375.
Phillis, J. W., and Wu, P. H., 1981, The role of adenosine and its nucleotides in central synaptic transmission, Prog. Neurobiol., 16:187–239.
Reddington, M., Lee, K. S., and Schubert, P., 1982, An A -receptor characterised by (3H)-cyclohexyladenosine binding, mediates the depression of evoked potentials in a rat hippocampus slice preparation, Neurosci. Lett., 28:275–279.
Rothmann, S. M., and Olney, J., 1987, Excitotoxicity and the NMDA receptor, Trends Neurol. Sci., 10:299–302.
Schubert, P., 1988, Modulation of synaptically evoked neuronal caclium fluxes by adenosine, in: “Neurotransmitters and cortical frunction. From molecules to mind,” M. Avoli, T. A. Reader, R. W. Dykes, and P, Gloor, eds., Plenum Press, New York, 471–483.
Stone, T. W., and Bartrup, J. T., 1989, Magnesium-dependency of presynaptic inhibition by adenosine, in: “Adenosine receptors in the nervous system,” J. A. Ribeiro, ed., Taylor & Francis, London, New York, Philadelphia, 87–95.
Wichman, T., Wictorin, K., Björklund, A., and Starke, K., 1988, Release of acetylcholine and its dopaminergic control in slices from striatal grafts in the ibotenic acid lesioned rat striatum, Naunyn-Schmiedeberg’s Arch. Pharmacol., 338:623–631.
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© 1991 Plenum Press, New York
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Porsche, E., Schwan, T. (1991). Depression of NMDA-Evoked Acetylcholine Release by Endogenous Adenosine in Striatum Slices. In: Kito, S., Segawa, T., Olsen, R.W. (eds) Neuroreceptor Mechanisms in Brain. Advances in Experimental Medicine and Biology, vol 287. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5907-4_20
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DOI: https://doi.org/10.1007/978-1-4684-5907-4_20
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