May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
LIGHT/DARK AND CIRCADIAN CLOCK DIFFERENTIALLY CONTROL THE EXTRACELLULAR LEVEL OF ADENOSINE IN THE MAMMALIAN RETINA.
Author Affiliations & Notes
  • C. Ribelayga
    Dept of Neurobiology, Univ of Alabama Sch of Med, Birmingham, AL
  • S.C. Mangel
    Dept of Neurobiology, Univ of Alabama Sch of Med, Birmingham, AL
  • Footnotes
    Commercial Relationships  C. Ribelayga, None; S.C. Mangel, None.
  • Footnotes
    Support  NIH Grant EY005102 and NSF Grant IBN–9819981
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 4644. doi:
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      C. Ribelayga, S.C. Mangel; LIGHT/DARK AND CIRCADIAN CLOCK DIFFERENTIALLY CONTROL THE EXTRACELLULAR LEVEL OF ADENOSINE IN THE MAMMALIAN RETINA. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4644.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Adenosine plays numerous modulatory roles in cell physiology in both normal and pathological conditions. Regulation of the extracellular level of adenosine (ADOe) is a complex process that includes two different sources. ADOe reflects efflux from the intracellular compartment via bidirectional adenosine transporters and/or the extracellular conversion of synaptically–released ATP via an ectonucleotidase pathway. In addition, clearance from the extracellular compartment requires reuptake and intracellular catabolism. A substantial body of indirect evidence suggests that adenosine acts as a neuromodulator in the vertebrate retina. To date, however, direct measurement and identification of the sources of ADOe in the retina are lacking. The present study was undertaken to clarify these issues. Methods: Rabbit neural retinas were isolated and maintained by superfusion (0.5 mL/min) at different times of the regular light/dark and circadian cycles. ADOe was measured from the medium by HPLC with fluorescence detection after conversion of the purine into the fluorescent compound 1–6N–etheno–adenosine. Results: ADOe was higher in the dark (+20%; P<0.001) than in dim light (low photopic range). Increasing light intensity further decreased ADOe. Application of 10 microM NBT, a specific adenosine membrane transport blocker, increased ADOe in the light and dark to a similar extent. In contrast, following the subsequent application of 1 mM GMP, an inhibitor of ectonucleotidase, ADOe decreased to an undetectable value in the light and dark. These observations indicate that the source of ADOe is extracellular, and that light and dark modulate the extracellular production of adenosine. ADOe was higher during the subjective night (+25%; P<0.001) compared to the subjective day indicating that ADOe is also controlled by a circadian clock. Application of NBT during the subjective night produced a significantly (P<0.001) smaller increase in ADOe compared to the subjective day, indicating that the intensity of the flux of adenosine toward the cytosol is reduced at night. Investigation is underway to determine whether the clock decreases adenosine transport activity at night or increases the intracellular content of adenosine at night, which might result from the clock–induced increase in cellular energy metabolism (Dmitriev & Mangel, 2001). Conclusions: In the mammalian retina, lighting conditions and a circadian clock modulate ADOe through different means, namely, by regulating the extracellular synthesis of adenosine and by modulating its inwardly–directed flux, respectively.

Keywords: adenosine • circadian rhythms • retina: neurochemistry 
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