Dominant localization of adenosine deaminase in leptomeninges and involvement of the enzyme in sleep

Adenosine is an endogenous hypnotic molecule. However, the mechanism by which the level of extracellular adenosine is regulated remains to be elucidated. We found by Northern hybridization and enzyme assay that ecto-5'-nucleotidase and adenosine deaminase (ADA), major enzymes responsible for the production and degradation of adenosine, respectively, were localized most abundantly in the leptomeninges within the rat brain. Immunohistochemical study showed that ADA was dominantly localized in arachnoid barrier and trabecular cells of the leptomeninges. In vivo microdialysis demonstrated that externally applied adenosine was rapidly metabolized by ADA to inosine in the subarachnoid space. Perfusion of an ADA inhibitor, coformycin, increased the extracellular adenosine level in the subarachnoid space under the rostral basal forebrain. When coformycin was continuously infused into the subarachnoid space, non-rapid eye movement sleep was increased with prolonged duration of the sleep episode. These results demonstrate that the leptomeninges control the extracellular level of adenosine in the subarachnoid space by their high 5'-nucleotidase and ADA activities and regulate non-rapid eye movement sleep. (C) 2003 Elsevier Inc. All rights reserved.