title: Enzymes of adenosine metabolism in the brain: diurnal rhythm and the effect of sleep deprivation.
abstract: Adenosine plays a role in promoting sleep, an effect that is thought to be mediated in the basal forebrain. Adenosine levels vary in this region with prolonged wakefulness in a unique way. The basis for this is unknown. We examined, in rats, the activity of the major metabolic enzymes for adenosine - adenosine deaminase, adenosine kinase, ecto- and cytosolic 5'-nucleotidase - in sleep/wake regulatory regions as well as cerebral cortex, and how the activity varies across the day and with sleep deprivation. There were robust spatial differences for the activity of adenosine deaminase, adenosine kinase, and cytosolic and ecto-5'-nucleotidase. However, the basal forebrain was not different from other sleep/wake regulatory regions apart from the tuberomammillary nucleus. All adenosine metabolic enzymes exhibited diurnal variations in their activity, albeit not in all brain regions. Activity of adenosine deaminase increased during the active period in the ventrolateral pre-optic area but decreased significantly in the basal forebrain. Enzymatic activity of adenosine kinase and cytosolic-5'-nucleotidase was higher during the active period in all brain regions tested. However, the activity of ecto-5'-nucleotidase was augmented during the active period only in the cerebral cortex. This diurnal variation may play a role in the regulation of adenosine in relationship to sleep and wakefulness across the day. In contrast, we found no changes specifically with sleep deprivation in the activity of any enzyme in any brain region. Thus, changes in adenosine with sleep deprivation are not a consequence of alterations in adenosine enzyme activity.
authors.affiliation: Center for Sleep and Respiratory Neurobiology, Division of Sleep Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. mirekmm@mail.med.upenn.edu
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Mackiewicz
authors.forename: Elena V
authors.initials: EV
authors.lastname: Nikonova
authors.forename: John E
authors.initials: JE
authors.lastname: Zimmerman
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Galante
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Jacqueline R
authors.initials: JR
authors.lastname: Cater
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Geiger
authors.forename: Allan I
authors.initials: AI
authors.lastname: Pack
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000378:metabolism; D000248:Adenosine Kinase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002940:Circadian Rhythm / Q000502:physiology*; D004798:Enzymes / Q000378:metabolism*; D008297:Male; D009708:Nucleotidases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012892:Sleep Deprivation / Q000201:enzymology*; D013997:Time Factors
chemical_list: D004798:Enzymes; D000248:Adenosine Kinase; D009708:Nucleotidases; C030287:nucleotidase; D015720:5'-Nucleotidase; D000243:Adenosine Deaminase; D000241:Adenosine