Abstract
In order to elucidate whether adenosine may be involved in the increase in cerebral blood flow (CBF) during functional hyperemia, cortical tissue levels of adenosine, inosine and hypoxanthine were measured in the cat following bicuculline (3 mg/kg)-induced seizure. In addition, the subcellular distribution of 5′-nucleotidase in the cortex was determined by histochemical techniques. Experiments were performed on anaesthetized and immobilized cats and tissue samples to be analyzed for the different purine compounds were obtained by freezing through the trepanized and non-trepanized skull. Control values for adenosine, inosine and hypoxanthine on the trepanized side were 1.31, 1.12 and 3.79 nmoles/g, respectively. The cortical content of adenosine increased to 3.85 nmoles/g, 15 s after beginning of seizure activity and remained elevated for 20 min. Inosine and hypoxanthine also increased, exhibiting highest values after 20 min. Values for adenosine and lactate were found to be generally higher when analysis was performed from tissue frozen through the intact skull bone. In all experiments the adenosine content correlated with lactate levels. From measurements of plasma concentrations of adenosine and inosine in the sinus sagittalis superior it is concluded that seizure is also accompanied by an enhanced release of adenosine from the brain. Localization of 5′-nucleotidase by electron-microscopic cytochemistry revealed that this enzyme is associated almost exclusively with plasma membranes of glial cell membranes including perivascular astrocytes. Thus high concentration of adenosine can be expected to accumulate locally in the brain cortex. In view of the well known increase in CBF during onset of seizure and the time course of adenosine formation, our findings support the view that adenosine may be involved in the initial phase of seizure-induced functional hyperemia of the brain.
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Schrader, J., Wahl, M., Kuschinsky, W. et al. Increase of adenosine content in cerebral cortex of the cat during bicuculline-induced seizure. Pflugers Arch. 387, 245–251 (1980). https://doi.org/10.1007/BF00580977
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DOI: https://doi.org/10.1007/BF00580977