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Quantitative correlation of dopamine-dependent adenylate cyclase with responses to levodopa in various mice.

We obtained 12 groups of mice with widely different neurological responses to levodopa by selecting them from different strains and submitting some of them to pretreatments. We scored the symptoms evoked by a standardized dose of levodopa in one subgroup from each group. We tested another subgroup for activation of an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by a standardized dose of dopamine added to homogenates of the caudate nuclei of the brains of these mice. Both sets of tests were performed randomly. When the accruing two sets of data were plotted against each other there emerged a straight line which fitted the data with a coefficient of correlation of 0.97 (P less than 0.0001). The dopamine-dependent activity of the adenylate cyclase of the brain was thus shown to be a determinant of the neurological responses of intact animals to a dopaminergic drug.