The hypothesis that uric acid induces hyperactivity by interacting with adenosine receptors in a manner analagous to caffeine was investigated. First, the extent to which uric acid and caffeine compete with the binding of the adenosine agonist ($\sp3$H) N$\sp6$-cyclohexyladenosine ($\sp3$H)CHA was examined in vitro. Only caffeine was found to inhibit ($\sp3$H) CHA binding in rat forebrain membranes in vitro. Second, possible developmental modification of adenosine receptors was examined by administering the uricase inhibitor allantoxanamide, which produces hyperuricemia, caffeine, or a control vehicle to young rats on Days 4 through 27 after birth. A significant increase in the number of binding sites for ($\sp3$H) CHA in the cortex of caffeine treated animals was observed. Non-significant increases in ($\sp3$H) CHA binding were observed in the striatum and thalamus. Chronic allantoxanamide, however, produced a non-significant decrease in ($\sp3$H) CHA binding. Fourteen days after withdrawal from treatment there were small non-significant increases in ($\sp3$H) CHA binding in both chronic caffeine and hyperuricemic rats. The results suggest that the mechanism by which uric acid induces hyperactivity is not through caffeine-sensitive adenosine receptors. Chronic caffeine administration in young rats results in an increase in the number of ($\sp3$H) CHA binding sites which does not appear to be permanent. Although a number of studies have suggested that uric acid acts like caffeine to increase activity, the present study clearly shows that the mode of action of uric acid is not like that of caffeine, at least as regards adenosine receptors / acase@tulane.edu
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_23146 |
| Date | January 1987 |
| Contributors | Hunter, Robert E (Author), Dohanich, Gary P (Thesis advisor) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Rights | Access requires a license to the Dissertations and Theses (ProQuest) database., Copyright is in accordance with U.S. Copyright law |
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