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The Journal of Neuroscience, January 5, 2005, 25(1):215-222; doi:10.1523/JNEUROSCI.3138-04.2005

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Behavioral/Systems/Cognitive
A Circadian Clock and Light/Dark Adaptation Differentially Regulate Adenosine in the Mammalian Retina

Christophe Ribelayga and Stuart C. Mangel

Department of Neurobiology, Civitan International Research Center, University of Alabama School of Medicine, Birmingham, Alabama 35294-0021

Although the purine adenosine acts as an extracellular neuromodulator in the mammalian CNS in both normal and pathological conditions and regulates sleep, the regulation of extracellular adenosine in the day and night is incompletely understood. To determine how extracellular adenosine is regulated, rabbit neural retinas were maintained by superfusion at different times of the regular light/dark and circadian cycles. The adenosine level in the superfusate, representing adenosine overflow from the retinas, and the adenosine level in retinal homogenates, representing adenosine content, were measured using HPLC with fluorescence detection in the absence or presence of blockers of adenosine transport and/or extracellular adenosine synthesis. We report that darkness, compared with illumination, increases the level of extracellular adenosine, and that a circadian clock also increases extracellular adenosine at night. In addition, we show that the darkness-evoked increase in the level of extracellular adenosine results primarily from an increase in the conversion of extracellular ATP into adenosine, but that the clock-induced increase at night results primarily from an increase in the accumulation of intracellular adenosine. We also show that a slightly hypoxic state increases adenosine content and overflow to an extent similar to that of the clock. Our findings demonstrate that the extracellular level of adenosine in the mammalian retina is differentially regulated by a circadian clock and the lighting conditions and is maximal at night under dark-adapted conditions. We conclude that adenosine is a neuromodulator involved in both circadian clock and dark-adaptive processes in the vertebrate retina.

Key words: adenosine; circadian rhythm; circadian clock; retina; dark adaptation; light adaptation

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Received May 4, 2004; revised November 11, 2004; accepted November 12, 2004.

This article has been cited by other articles:

				B. D. Clark, Z. L. Kurth-Nelson, and E. A. Newman Adenosine-Evoked Hyperpolarization of Retinal Ganglion Cells Is Mediated by G-Protein-Coupled Inwardly Rectifying K+ and Small Conductance Ca2+-Activated K+ Channel Activation J. Neurosci., September 9, 2009; 29(36): 11237 - 11245. [Abstract] [Full Text] [PDF]

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				E. A. Newman Calcium Increases in Retinal Glial Cells Evoked by Light-Induced Neuronal Activity J. Neurosci., June 8, 2005; 25(23): 5502 - 5510. [Abstract] [Full Text] [PDF]

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