Dopamine D‐1 Receptor and Cyclic AMP‐Dependent Phosphorylation in Parkinson's Disease

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Abstract
D‐1 and D‐2 receptor densities, evaluated respectively by [3H]SCH 23390 and [3H]spiperone binding, and DARPP‐32 (dopamine and adenosine 3′:5′‐monophos‐phate‐regulated phosphoprotein—32K) concentrations, were studied in the brains of control and parkinsonian subjects postmortem. D‐2 receptor density was unchanged in the putamen of parkinsonian patients. D‐1 receptor density was unchanged in the putamen and substantia nigra pars reticulata (SNR) of parkinsonian patients, but decreased by 28% in the substantia nigra pars compacta (SNC). DARPP‐32, which is localized in the same structures as D‐1 receptors of which it is thought to represent the intracellular messenger, decreased by 45% in the putamen, 66% in the SNR, and 79% in the SNC. The decrease in D‐1 receptors in the SNC may be due to degeneration of pallidonigral GABAergic neurons, but some of the D‐1 receptors may be on the nigrostriatal dopaminergic neurons themselves. The dissociation between the alteration of D‐1 receptor densities and DARPP‐32 concentrations in both the striatum and substantia nigra, which are of the same order in the two structures, may be an index of functional hypoactivity of D‐1 neurotransmission.