Adenosine is not a neurotransmitter but rather a paracrine neuromodulator. This obviously does not mean that adenosine is not biologically important—it just means that we must think differently about its role compared to, for example, dopamine or noradrenaline.
There are two main ways in which adenosine levels can increase: it can be released from cells primarily by means of bi-directional transporters (Thorn and Jarvis 1996; Griffiths et al. 1997; Dunwiddie and Diao 2000), or it can be formed from breakdown of extracellular adenine nucleotides by means of a multitude of ecto-nucleotidases (Zimmermann 2000). Judging by the large number of studies using techniques such as microdialysis adenosine levels are likely to be in the range of 20 to 300 nM (Ballarin et al. 1991; Baranowski and Westenfelder 1994; Pazzagli etal. 1995; Huston etal. 1996; Porkka-Heiskanen etal. 1997). Furthermore, these studies show that adenosine levels can be altered by hypoxia, by drugs and by behavioural states. Thus, cells in the nervous system will always be exposed to adenosine at concentrations close to 100 nM. Locally, levels can increase in response to synaptic activity, to increased metabolic demand and to several other stimuli. Globally, levels may change as a consequence of decreased supply of oxygen or glucose. However, compared to many transmitters, changes in adenosine are likely to occur over wider domains and with a slower time course.
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