Brain benzodiazepine receptor binding and purine concentration in Lesch-Nyhan syndrome

Benzodiazepine receptor [( 3H]flunitrazepam) binding and purine concentration were measured in autopsied cerebral cortex of 4 patients who died with Lesch-Nyhan syndrome. Receptor density was normal in all 4 regions of Lesch-Nyhan cortex examined. However, an enhancement of benzodiazepine receptor affinity (25% reduction in Kd) was found in well-washed parietal and occipital cortex homogenates. Maximal gamma-aminobutyric acid (GABA) stimulation of [3H]flunitrazepam binding was normal in temporal, parietal and occipital cortex but markedly reduced (by 50-80%) in frontal cortex. Increased sensitivity to hypoxanthine inhibition (30% reduction in Ki) was also observed in parietal cortex. The concentrations of the purines hypoxanthine, xanthine and inosine in Lesch-Nyhan parietal cortex were about twice the values measured in control material matched for postmortem time. We suggest that the above-normal concentrations of purines estimated to be present in Lesch-Nyhan brain may be sufficient to significantly affect the ability of the benzodiazepine receptor to modulate GABA-mediated brain mechanisms.