3H-spiperone binding to lymphocytes fails in the differential diagnosis of de novo Parkinson syndromes

Abstract

In order to investigate the diagnostic value of 3H-spiperone binding capacity to lymphocytes in the differential diagnosis of de novo Parkinson's disease (idiopathic Parkinson syndrome, PD), we performed a double blind prospective study of spiperone binding capacity of 123 patients and 23 healthy control persons, belonging to different diagnostic groups (PD, Parkinsonian syndrome due to vascular lesions, multiple system atrophy [MSA], essential tremor). Diagnoses were based on medical history, clinical examination, CT or MRI scan, acute response to dopamimetic drugs, one year follow up, and long term response to L-DOPA treatment. Spiperone binding was assayed using ten different concentrations (0.03-3 nmol) in absence or presence of 1 mumol (+)-butaclamol to determine nonspecific binding. There was no significant difference in spiperone binding between patients with PD not treated with L-DOPA, and patients with other basal ganglia disorders including parkinsonian syndrome due to vascular lesions, multiple system atrophy, or progressive supranuclear palsy, and age matched controls. Binding was significantly higher in parkinsonian patients with PD treated with L-DOPA and patients with essential tremor. It is concluded that at present 3H-spiperone binding gives no further information in the differential diagnosis of de novo Parkinson's disease.

Increased expression of dopamine receptors on lymphocytes in Parkinson's disease

“…35 The problem of changes in dopamine receptor expression by PBL in PD has been addressed by some authors who have reported a decrease in [ 3 H]spiperone binding 36 or no modifications. 20 A reduction in D3 receptor density on PBL has been documented more recently. 37 However, the heterogeneity of the PD population in this last study, which included both treated and untreated patients, may account for the discrepancies between those results and ours, because treatment with dopaminergic drugs significantly alters the expression of dopamine receptors on PBL.…”

“…16 However, the assay of [ 3 H]spiperone binding to PBL in neuropsychiatric disorders provided conflicting results because, as later demonstrated, this ligand does not interact with specific membrane receptors but is taken up into lysosomes in a nonspecific way. [17][18][19][20][21] Only recently have molecular biology and binding studies with specific radioligands demonstrated that PBL express dopamine D3, D4, and D5 receptor subtypes. [22][23][24][25][26][27] In this study, we compared dopamine D1-like and D2-like receptor binding to PBL from de novo PD patients with that of patients affected by other neurodegenerative diseases and of healthy control subjects using the dopamine D1-like receptor antagonist [ 3 H]SCH 23390 and the dopamine D2-like receptor agonist [ 3 H]7OH-DPAT as ligands.…”

Reduced Gs protein function and Gαs levels in leukocytes of patients with Parkinson's disease

“…Muscarinic receptor-coupled G, protein function was found to be similar in patients with Parkinson's disease and in control subjects. As previous studies (43,45,46) have failed to observe significant changes in receptor levels in MNLs of patients with Parkinson's disease, these findings of reduced function of P-adrenergic and dopamine receptor-coupled G, protein function suggest alterations distal to these receptors, at the level of the signal-transducing G, protein. Indeed, assessment of Gprotein levels in human MNLs through immunoblot analysis by using polyclonal antibodies against various Ga subunits shows that the 45-kDa species of G a s is significantly reduced in patients with Parkinson's disease in comparison with control subjects, whereas other non-G, proteins (Gai, Ga,) did not differ between patients with Parkinson's disease and control subjects.…”

“…A decreased binding of spiperone to lymphocytes in patients with Parkinson's disease was reported as early as 1980 (42) and confirmed by later studies. However, a larger scale experiment indicated that spiperone binding to lymphocytes failed in the diagnosis of de novo Parkinson's disease (43). Of crucial importance in this regard is the more recent finding that spiperone labels v receptors rather than dopamine D, receptors in rat and human lymphocytes (44).…”