High-affinity binding sites for neuroleptic drugs in human peripheral blood lymphocytes and their relation to dopamine receptors

Vile, John M.; Strange, Philip G.

doi:10.1016/0006-2952(94)00426-m

Cited by 17 publications

(14 citation statements)

References 33 publications

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“…30 [22][23][24][25][26][27] whereas no evidence exists of the expression of dopamine D1 and D2 receptor subtypes. 33,34 Several neurologic and psychiatric disorders are characterized by central dopaminergic dysfunction. Their diagnosis is still almost entirely clinical.…”

Section: Discussionmentioning

confidence: 99%

“…Until recently, however, no conclusive evidence had emerged demonstrating that highaffinity binding sites for neuroleptic drugs on PBL do represent dopamine receptors. 33 In fact, one major problem is the low density of putative dopamine receptors on PBL. Furthermore, [ 3 H]spiperone or [ 3 H]nemonapride, widely used in previous studies, do not provide a reliable receptorial assay because of their lipophilic properties, low specific/nonspecific binding ratio, and lack of stereospecificity.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, [ 3 H]spiperone or [ 3 H]nemonapride, widely used in previous studies, do not provide a reliable receptorial assay because of their lipophilic properties, low specific/nonspecific binding ratio, and lack of stereospecificity. 33,34 In addition, most studies have used radioligand concentrations which have been remarkably higher than Kd values, 33 thus hampering the detection of specific dopamine receptor binding. Thus, we used the selective dopamine D1-like receptor antagonist [ 3 H]SCH 23390 and the preferential dopamine D3 receptor agonist [ 3 H]7OH-DPAT at the lowest concentration allowing the optimal specific/nonspecific binding ratio.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

et al. 1999

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Dopamine D1‐like and D2‐like receptors on peripheral blood lymphocytes (PBL) were assayed in 50 de novo patients with idiopathic Parkinson's disease (PD), in 36 neurologic control subjects (multiple‐system atrophy, n = 16; essential tremor, n = 10; other neurodegenerative diseases, n = 10), and in 26 healthy control subjects by radioligand binding assay techniques using [3H]SCH 23390 and [3H]7OH‐DPAT as ligands. Patients with PD revealed a higher density (Bmax) of dopamine D1‐like (p <0.001) and D2‐like (p <0.00001) receptors on PBL than either neurologic or healthy control subjects, whereas no differences in Bmax were observed among patients affected by other neurologic diseases and healthy control subjects. The affinity (Kd) of both radioligands was similar in the groups investigated. The pharmacologic profile of [3H]SCH 23390 and [3H]7OH‐DPAT binding was consistent with the labeling of dopamine D5 and D3 receptor subtypes, respectively. Twenty‐five of the 50 patients with PD were retested after 3 months of therapy with levodopa or bromocriptine. Both treatments reduced the density of D1‐like (p <0.001) and D2‐like (p <0.001) receptors on PBL to values comparable to those of control subjects. The increased density of D1‐like and D2‐like receptors on PBL in de novo PD patients may represent an upregulation mechanism resulting from the diffuse impairment of the dopaminergic system in PD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 1999

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“…Different data show that human blood lymphocytes present and express some DA receptors, in particular D3, D4 and D5 subtypes [16][17][18][19], produces DA [20][21][22][23] and possess the catecholamine biosynthethic enzyme, tyrosine hydroxylase [23,24]. The presence of a cocaine-sensitive DAT in human lymphocytes identified by means of 3 H-DA reuptake assays was also reported [25], although this finding was criticized again for the impact of platelet contamination [26].…”

Section: Introductionmentioning

confidence: 84%

Presence and Characterization of the Dopamine Transporter in Human Resting Lymphocytes

et al. 2007

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The paucity of information on the presence of the dopamine transporter (DAT) in blood cells, prompted us to explore it in human resting lymphocytes by means of the binding of 3H-WIN 35,428, a compound which is currently considered the most selective ligand for labelling this protein, and by means of the specific reuptake of 3H-dopamine (3H-DA). Lymphocytes were obtained by 15 healthy subjects. The results showed the presence of a specific and saturable binding of 3H-WIN 35,428, which labelled one site only. A specific 3H-DA reuptake was also measured. The pharmacological characterization of both binding and reuptake was overlapping. These findings would indicate that human resting lymphocytes carry the DAT, whose functions in periphery are still unknown.

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Expression of Dopaminergic Receptors on Human CD4+ T Lymphocytes: Flow Cytometric Analysis of Naive and Memory Subsets and Relevance for the Neuroimmunology of Neurodegenerative Disease

Kuštrimović

Rasini

Legnaro

et al. 2014

J Neuroimmune Pharmacol

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Dopamine (DA) is a crucial transmitter in the neuroimmune network, where it contributes to the nervous system-immune system interplay as well as in the communication among immune cells. DA acts through five different dopaminergic receptors (DR) grouped into two families: the D1-like (D1 and D5) and the D2-like (D2, D3 and D4). By use of 5-color flow cytometric analysis, we examined the expression of DR on human CD4+ naive T lymphocytes (CD3+CD4+CD45RA+CCR7+), central memory (TCM, CD3+CD4+CD45RA-CCR7+) and effector memory T cells (TEM, CD3+CD4+CD45RA-CCR7-). In addition, in cultured CD4+ T cells we investigated the changes in DR expression induced by stimulation with antiCD3/antiCD28 antibodies. Results showed that CD4+ T cells always expressed all the five DR: D1-like DR were identified on average on 11.6-13.1 % and D2-like DR on 3.1-8.1 % of the cells. DR on CD4+ naive T cells, TCM, and TEM had distinct expression patterns: naive T cells expressed more D1-like than D2-like DR, which on the contrary were increased in TCM and TEM cells. In cultured CD4+ T cells stimulation with anti-CD3/anti-CD28 antibodies increased the expression of D1-like DR by 71-84 % and of D2-like DR by 55-97 %. The frequency of DR was higher in apoptotic cells in comparison to viable cells, however stimulation increased all DR on viable cells, without affecting their expression on apoptotic cells. The present results contribute to unravel the complexity of dopaminergic pathways in human CD4+ T lymphocytes, suggesting their involvement in memory functions as well as in apoptotic processes. In view of the role of CD4+ memory T cells in neuroinflammation and neurodegeneration during Parkinson's disease, the relevance of these findings must be assessed in the clinical setting.

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High-affinity binding sites for neuroleptic drugs in human peripheral blood lymphocytes and their relation to dopamine receptors

Cited by 17 publications

References 33 publications

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

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

Presence and Characterization of the Dopamine Transporter in Human Resting Lymphocytes

Expression of Dopaminergic Receptors on Human CD4+ T Lymphocytes: Flow Cytometric Analysis of Naive and Memory Subsets and Relevance for the Neuroimmunology of Neurodegenerative Disease

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