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Physiologic and Metabolic Regulation of Adenosine: Mechanisms

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Adenosine

Abstract

Adenosine is the purine nucleoside core of adenosine triphosphate (ATP), a molecule that allows biological energy storage, and changes in intracellular adenosine levels are thought to reflect the energy state of the cell: during net ATP consumption, adenosine accumulates. Via adenosine A1 receptors, increases in extracellular adenosine can decrease neuronal excitability rapidly. Accordingly, the interplay between energy use and neuronal activity provides a feedback system by which increased energy utilization can decrease energy demand. This is, however, a simplistic view of the regulation of adenosine in the nervous system. Advances in adenosine measurement and genetic tools to dissect the sources of adenosine have lent insight into a dynamic physiological regulation of adenosine and a bevy of cellular changes which alter adenosine tone. Here we examine recent work probing specific physiologic and metabolic changes which influence adenosine (and thus synaptic transmission), focusing primarily on the hippocampus. We summarize the current understanding of how tonic extracellular adenosine levels are set and highlight unanswered questions. Regarding dynamic physiological regulation, we outline how stimuli such as pH, neuronal activity, altered metabolism, and hypoxia can modulate adenosine levels. Using specific examples, we describe how changes in adenosine may act to normalize or restore physiologic and metabolic balance.

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Acknowledgments

We thank the National Institutes of Health, National Science Foundation, Tufts University School of Medicine and Trinity College for their support.

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  1. Neuroscience Department, Tufts University Medical School, Boston, MA, USA

    Chris G. Dulla

  2. Psychology Department and Neuroscience Program, Trinity College, Hartford, CT, USA

    Susan A. Masino

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Correspondence to Chris G. Dulla .

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  1. Trinity College, 300 Summit Street, LSC 208, Hartford, 06106, USA

    Susan Masino

  2. Legacy Research Institute, Portland, OR,, 1225 NE 2nd Avenue, Portland, 97232, USA

    Detlev Boison

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Dulla, C.G., Masino, S.A. (2013). Physiologic and Metabolic Regulation of Adenosine: Mechanisms. In: Masino, S., Boison, D. (eds) Adenosine. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3903-5_5

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