Enzymes of adenosine metabolism in the brain: diurnal rhythm and the effect of sleep deprivation

被引:45
作者
Mackiewicz, M
Nikonova, EV
Zimmerman, JE
Galante, RJ
Zhang, L
Cater, JR
Geiger, JD
Pack, AI
机构
[1] Univ Penn, Dept Med, Div Sleep Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Med, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA
[3] Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada
关键词
adenosine; adenosine metabolism; basal forebrain; enzymes; sleep homeostasis;
D O I
10.1046/j.1471-4159.2003.01687.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:348 / 357
页数:10
相关论文
共 30 条
[11]  
Kong JM, 2002, J NEUROSCI, V22, P5581
[12]  
LIN BB, 1988, MOL PHARMACOL, V34, P501
[13]   Effect of lesions of the ventrolateral preoptic nucleus on NREM and REM sleep [J].
Lu, J ;
Greco, MA ;
Shiromani, P ;
Saper, CB .
JOURNAL OF NEUROSCIENCE, 2000, 20 (10) :3830-3842
[14]   Simultaneous assessment of ecto- and cytosolic-5′-nucleotidase activities in brain micropunches [J].
Mackiewicz, M ;
Geiger, JD ;
Pack, AI .
JOURNAL OF NEUROSCIENCE METHODS, 2000, 104 (01) :9-18
[15]   Activity of adenosine deaminase in the sleep regulatory areas of the rat CNS [J].
Mackiewicz, M ;
Nikonova, EV ;
Bell, CC ;
Galante, RJ ;
Zhang, L ;
Geiger, JD ;
Pack, AI .
MOLECULAR BRAIN RESEARCH, 2000, 80 (02) :252-255
[16]  
MEGHJI P, 1991, ADENOSINE NERVOUS SY, P25
[17]   CAFFEINE AND THE CENTRAL-NERVOUS-SYSTEM - MECHANISMS OF ACTION, BIOCHEMICAL, METABOLIC AND PSYCHOSTIMULANT EFFECTS [J].
NEHLIG, A ;
DAVAL, JL ;
DEBRY, G .
BRAIN RESEARCH REVIEWS, 1992, 17 (02) :139-169
[18]   SOLUBLE 5'-NUCLEOTIDASE ACTIVITIES IN RAT-BRAIN [J].
ORFORD, M ;
MAZURKIEWICZ, D ;
SAGGERSON, D .
JOURNAL OF NEUROCHEMISTRY, 1991, 56 (01) :141-146
[19]  
Paxinos G., 1986, RAT BRAIN STEREOTAXI, Vsecond
[20]   Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep:: An in vivo microdialysis study [J].
Porkka-Heiskanen, T ;
Strecker, RE ;
McCarley, RW .
NEUROSCIENCE, 2000, 99 (03) :507-517