Adenosine as a neuromodulator

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Evidence from many sources implicates adenosine in brain function. Whether adenosine is a neurotransmitter or neuromodulator is unclear. Indeed, the distinction between neurotransmitters and neuromodulators is becoming increasingly fuzzy. The one item of information most needed to clarify the role of adenosine in the brain is histochemical evidence of its localization. Even though metabolic pools of adenosine occur in all cells in the brain, 'adenosine-ergic' neurons might possess especially high levels compared to surrounding cells. If adenosine is concentrated in specific neuronal populations, it may function as a 'classical' neurotransmitter or, like the neuropeptides, it may regulate the release of other transmitters. Alternatively, adenosine may be synthesized on neuronal membranes where it exerts its effects, functioning very much like the prostaglandins. Some evidence favors this latter view. The localization of adenosine A1 receptors resembles that of 5'-nucleotidase, a membrane-associated enzyme. Adenosine A1 receptors are associated with parallel fibers of cerebellar granule cells and retinal ganglion cell afferent nerve terminals to the superior colliculus. Axoaxonic synapses for putative adenosinergic neurons have not been described in either place. If 5'-nucleotidase synthesizes adenosine on membranes of cerebellar parallel fibers, then the adenosine-synthesizing system and the adenosine receptors would be contained on the same axon terminals. Endogenous adenosine accumulates rapidly even in extensively washed synaptic membranes separated from RNA- or DNA-containing particles that might generate adenosine. This further supports the notion that adenosine may be generated on membranes at the site of its actions. On the other hand, a strong case for adenosinergic neurons comes from the lesion studies showing that in the corpus striatum 70% of endogenous adenosine occurs on intrinsic neurons and another 20% occurs on terminals of the nigrostriatal dopamine pathway. Resolution of this important question awaits newer experimental approaches.

Original languageEnglish (US)
Pages (from-to)103-124
Number of pages22
JournalAnnual review of neuroscience
VolumeVOL. 8
StatePublished - 1985

ASJC Scopus subject areas

  • Neuroscience(all)

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