Activity of adenosine deaminase in the sleep regulatory areas of the rat CNS

There are data to support the notion that adenosine (ADO, a neuromodulator in the CNS, is an important regulator of sleep homeostasis. It has been dem onstrated that ADO agonists and antagonists strongly impact upon sleep. In addition, the level of adenosine varies across the sleep/wake cycle and inc reases following sleep deprivation. Adenosine deaminase (ADA) is a key enzy me involved in the metabolism of ADO. We questioned, therefore, whether the re are differences in adenosine deaminase activity in brain regions relevan t to sleep regulation. We found that ADA exhibits a characteristic spatial pattern of activity in the rat CNS with the lowest activity in the parietal cortex and highest in the region of the tuberomammillary nucleus (15.0+/-4 .8 and 63.4+/-28.0 nmoles/mg protein/15 min. mean+/-S.D., respectively). Th ere were significant differences among the brain regions by one-way ANOVA ( F=31.33, df=6,123, P=0.0001). The regional differences in ADA activity corr elate with variations in the level of its mRNA. This suggests that spatial differences in ADA activity are the result of changes in the expression of the ADA gene. We postulate that adenosine deaminase plays an important role in the mechanism that controls regional concentration of adenosine in the brain and thus, it is a part of the sleep-wake regulatory mechanism. (C) 20 00 Elsevier Science B.V. All rights reserved.