Norstrand I F, Debons A F, Libbin R M, Slade W R
Enzyme. 1983;29(1):61-5. doi: 10.1159/000469605.
Since inosine is an inhibitory ligand for benzodiazepine binding, and since several of the purine enzymes have a specific localization, it was hypothesized that the unique distribution of benzodiazepine receptors may be dependent on the regional concentrations and specific actions of these enzymes in increasing or decreasing the amount of inosine. To test the above theory, the binding of 3H-flunitrazepam to receptors was studied on homogenates of various regions of autopsied human brain before and after treatment with irreversible potent inhibitors of the purine enzymes guanine deaminase and adenosine deaminase. As predicted, inhibition of guanase, which metabolizes guanine and hypoxanthine to xanthine, caused a marked inhibition of binding in the cerebral cortex and midbrain, where there is an abundance of enzyme, and only slight change in binding in the medulla, cerebellum or pons, where there is little enzyme. When adenosine deaminase, which converts adenosine to inosine, was inhibited, there was increased binding, with as much as a 4-fold increase in the frontal lobe, and very little effect in the cerebellum, medulla or temporal lobe.
