Summary
Considerable evidence indicates a modulatory role for adenosine (A) on synaptic transmission in both peripheral and central nervous systems. In vivo and in vitro experiments in the rat hippocampus demonstrate the axonal transport of A derivatives to nerve endings with subsequent stimulus-dependent release. Analysis of the material released from central tissues on electrical stimulation indicates that at least a proportion of the A derivatives collected are recovered in the form of nucleotides, together with A and several breakdown products. This observation, in conjunction with the demonstrable release of ATP from nerve endings, suggests the release of adenine nucleotides with subsequent extracellular breakdown to produce A.
A has been shown to depress both spontaneous and evoked potentials in central neurons. In hippocampal slices the addition of A to the superfusion medium in μM concentrations leads to a reduction in the amplitude of evoked synaptic potentials. Pharmacological studies of the effects of various nucleoside derivatives on synaptic activity in this system indicate that this effect is mediated via an Al-adenosine receptor which can be distinguished from that mediating a stimulation of cyclic AMP synthesis (the A2-receptor). Taken together, these observations suggest that the modulatory effect of adenine derivatives in the CNS depends on (1) the release of nucleotides and subsequent breakdown to A and (2) the presence of Al-adenosine receptors.
The last step in the production of A from nucleotides is catalyzed by 5′-nucleotidase. EM-cytochemical studies demonstrate 5′-nucleotidase in association with several structures including astrocytic processes surrounding nerve endings and with some synapses. Therefore, the availability of 5′-nucleotidase is considered an important factor determining the production of A.
The availability of Al-adenosine receptors is a further factor determining the physiological effectiveness of A. The amplitude of the A-induced depression of synaptic transmission in the rat hippocampus is related to the local concentration of Al-receptors estimated using an in vitro ligand binding assay.
These considerations lead to the conclusion that the release of nucleotides, their breakdown to A via 5′-nucleotidase and the availability of A1-adenosine receptors are important factors determining the overall neuromodulatory effect of adenine derivatives.
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Kreutzberg, G.W., Reddington, M., Lee, K.S., Schubert, P. (1983). Adenosine: Transport, Function and Interaction with Receptors in the CNS. In: Goldstein, M., Jellinger, K., Riederer, P. (eds) Basic Aspects of Receptor Biochemistry. Journal of Neural Transmission, vol 18. Springer, Vienna. https://doi.org/10.1007/978-3-7091-4408-4_10
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DOI: https://doi.org/10.1007/978-3-7091-4408-4_10
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