Guanyl nucleotide interactions with dopaminergic binding sites labeled by [3H]spiroperidol in human caudate and putamen: guanyl nucleotides enhance ascorbate-induced lipid peroxidation and cause an apparent loss of high affinity binding sites.

The human caudate and putamen contain two high affinity binding sites for [3H]spiroperidol. Both of these affinity states exhibit dopaminergic selectivity. Ascorbic acid, at 0.1 mM, induces a slow loss of the low affinity component of [3H]spiroperidol binding in these tissues. The addition of guanyl nucleotides to the ascorbate produces a more rapid loss of [3H]spiroperidol binding which includes a loss of the highest affinity state for [3H]spiroperidol. Ascorbate induces lipid peroxidation in human caudate and putamen, an effect that is further enhanced by guanyl and inosine nucleotides. In the absence of ascorbate, guanyl nucleotides have no effect on [3H]spiroperidol binding but do decrease the affinity of dopamine at each affinity state greater than 60-fold. In the absence of ascorbate, guanyl nucleotides apparently decrease agonist affinity at human brain dopamine2-binding sites without causing an interconversion of agonist affinity states.