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 demonstrated that ADO agonists and antagonists strongly impact upon sleep. In addition, the level of adenosine varies across the sleep/wake cycle and increases following sleep deprivation. Adenosine deaminase (ADA) is a key enzyme involved in the metabolism of ADO. We questioned, therefore, whether there are differences in adenosine deaminase activity in brain regions relevant 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). There 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 correlate 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) 2000 Elsevier Science B.V.